Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans

Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small‐conductance Ca2+‐activ...

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Published inNeurogastroenterology and motility Vol. 24; no. 9; pp. 844 - 852
Main Authors Grover, M., Bernard, C. E., Pasricha, P. J., Parkman, H. P., Abell, T. L., Nguyen, L. A., Snape, W., Shen, K. R., Sarr, M., Swain, J., Kendrick, M., Gibbons, S., Ordog, T., Farrugia, G.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.09.2012
Subjects
Adult
Antibodies
Biopsy
Case-Control Studies
Cell body
Cytology
Diabetes Complications - metabolism
Diabetes mellitus
Enteric nervous system
Female
fibroblast-like cells
Ganglia
Gastric Emptying
gastroparesis
Gastroparesis - metabolism
Humans
Immunohistochemistry
Interstitial cells
interstitial cells of Cajal
Male
Muscle, Smooth - cytology
Muscle, Smooth - metabolism
myenteric plexus
Myenteric Plexus - metabolism
Nervous system
platelet-derived growth factor receptor
Platelet-derived growth factor receptors
Potassium channels (calcium-gated)
Receptor, Platelet-Derived Growth Factor alpha - metabolism
Small-Conductance Calcium-Activated Potassium Channels - metabolism
Smooth muscle
Stomach - cytology
Stomach - metabolism
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Abstract Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small‐conductance Ca2+‐activated K+ channels (SK3). In mice, platelet‐derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα‐immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods  Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results  Intramuscular PDGFRα‐ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3–4 processes and formed networks, often around ganglia. All SK3‐ir cell structures showed complete overlap with PDGFRα‐ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences  In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
AbstractList Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced.BACKGROUNDEmerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced.Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified.METHODSFull thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified.Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients.KEY RESULTSIntramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients.In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.CONCLUSIONS & INFERENCESIn conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small‐conductance Ca2+‐activated K+ channels (SK3). In mice, platelet‐derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα‐immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods  Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results  Intramuscular PDGFRα‐ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3–4 processes and formed networks, often around ganglia. All SK3‐ir cell structures showed complete overlap with PDGFRα‐ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences  In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
Background Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor alpha (PDGFR alpha ) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFR alpha -immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFR alpha staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFR alpha -ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFR alpha -ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFR alpha identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small‐conductance Ca 2+ ‐activated K + channels (SK3). In mice, platelet‐derived growth factor receptor α (PDGFR α ) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFR α ‐immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods  Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFR α staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results  Intramuscular PDGFR α ‐ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3–4 processes and formed networks, often around ganglia. All SK3‐ir cell structures showed complete overlap with PDGFR α ‐ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences  In conclusion, PDGFR α identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.
Author Pasricha, P. J.
Parkman, H. P.
Sarr, M.
Bernard, C. E.
Nguyen, L. A.
Gibbons, S.
Shen, K. R.
Kendrick, M.
Farrugia, G.
Abell, T. L.
Snape, W.
Grover, M.
Ordog, T.
Swain, J.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22650155$$D View this record in MEDLINE/PubMed
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PublicationTitle Neurogastroenterology and motility
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References Zhang Y, Carmichael SA, Wang XY, Huizinga JD, Paterson WG. Neurotransmission in lower esophageal sphincter of W/Wv mutant mice. Am J Physiol Gastrointest Liver Physiol 2010; 298: G14-24.
Vanderwinden JM, Rumessen JJ, De Laet MH, Vanderhaeghen JJ, Schiffmann SN. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract. Cell Tissue Res 2000; 302: 145-53.
Iino S, Nojyo Y. Immunohistochemical demonstration of c-Kit-negative fibroblast-like cells in murine gastrointestinal musculature. Arch Histol Cytol 2009; 72: 107-15.
Vanderwinden JM, Rumessen JJ, de Kerchove d'Exaerde A Jr et al. Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease. Cell Tissue Res 2002; 310: 349-58.
Cobine CA, Hennig GW, Kurahashi M, Sanders KM, Ward SM, Keef KD. Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter. Cell Tissue Res 2011; 344: 17-30.
Faussone-Pellegrini MS, Grover M, Pasricha P et al. Ultrastructural differences between diabetic and idiopathic gastroparesis: The NIDDK gastroparesis clinical research consortium (GpCRC). J Cell Mol Med 2011; doi: 10.1111/j.1582-4934.2011.01451.x.
Groneberg D, Konig P, Koesling D, Friebe A. Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle. Gastroenterology 2011; 140: 1608-17.
Ro S, Hatton WJ, Koh SD, Horowitz B. Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle. Am J Physiol Gastrointest Liver Physiol 2001; 281: G964-73.
Fujita A, Takeuchi T, Jun H, Hata F. Localization of Ca2+-activated K+ channel, SK3, in fibroblast-like cells forming gap junctions with smooth muscle cells in the mouse small intestine. J Pharmacol Sci 2003; 92: 35-42.
Hoch RV, Soriano P. Roles of PDGF in animal development. Development 2003; 130: 4769-84.
Grover M, Farrugia G, Lurken MS et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology 2011; 140: 1575-85. e8.
Ueno T, Duenes JA, Zarroug AE, Sarr MG. Nitrergic mechanisms mediating inhibitory control of longitudinal smooth muscle contraction in mouse small intestine. J Gastrointest Surg 2004; 8: 831-41.
Rumessen JJ, Thuneberg L. Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers. Gastroenterology 1991; 100: 1417-31.
Hosseini R, Benton DC, Dunn PM, Jenkinson DH, Moss GW. SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones. J Physiol 2001; 535: 323-34.
Grunnet M, Jespersen T, Angelo K et al. Pharmacological modulation of SK3 channels. Neuropharmacology 2001; 40: 879-87.
Karlsson L, Lindahl P, Heath JK, Betsholtz C. Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 2000; 127: 3457-66.
Kashyap P, Farrugia G. Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years. Gut 2010; 59: 1716-26.
Vanderwinden JM, Rumessen JJ, De Laet MH, Vanderhaeghen JJ, Schiffmann SN. CD34+ cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal. Lab Invest 1999; 79: 59-65.
Iino S, Horiguchi K, Nojyo Y. Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide-sensitive guanylate cyclase in the guinea-pig gastrointestinal tract. Neuroscience 2008; 152: 437-48.
El-Yazbi AF, Cho WJ, Boddy G, Schulz R, Daniel EE. Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles. Am J Physiol Gastrointest Liver Physiol 2006; 290: G394-403.
Kurahashi M, Zheng H, Dwyer L, Ward SM, Don Koh S, Sanders KM. A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles. J Physiol 2011; 589: 697-710.
Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 1996; 93: 12008-13.
Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008; 22: 1276-312.
Horiguchi K, Komuro T. Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine. J Auton Nerv Syst 2000; 80: 142-7.
Bond CT, Sprengel R, Bissonnette JM et al. Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. Science 2000; 289: 1942-6.
Ward SM, Morris G, Reese L, Wang XY, Sanders KM. Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters. Gastroenterology 1998; 115: 314-29.
Streutker CJ, Huizinga JD, Campbell F, Ho J, Riddell RH. Loss of CD117 (c-kit)- and CD34-positive ICC and associated CD34-positive fibroblasts defines a subpopulation of chronic intestinal pseudo-obstruction. Am J Surg Pathol 2003; 27: 228-35.
Choi KM, Gibbons SJ, Roeder JL et al. Regulation of interstitial cells of Cajal in the mouse gastric body by neuronal nitric oxide. Neurogastroenterol Motil 2007; 19: 585-95.
Farrugia G. Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil 2008; 20(Suppl. 1): 54-63.
Rumessen JJ, Thuneberg L, Mikkelsen HB. Plexus muscularis profundus and associated interstitial cells. II. Ultrastructural studies of mouse small intestine. Anat Rec 1982; 203: 129-46.
Vittal H, Farrugia G, Gomez G, Pasricha PJ. Mechanisms of disease: the pathological basis of gastroparesis--a review of experimental and clinical studies. Nat Clin Pract Gastroenterol Hepatol 2007; 4: 336-46.
Fujita A, Takeuchi T, Saitoh N, Hanai J, Hata F. Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract. Am J Physiol Cell Physiol 2001; 281: C1727-33.
Spencer NJ, Hennig GW, Smith TK. Stretch-activated neuronal pathways to longitudinal and circular muscle in guinea pig distal colon. Am J Physiol Gastrointest Liver Physiol 2003; 284: G231-41.
Sivarao DV, Mashimo HL, Thatte HS, Goyal RK. Lower esophageal sphincter is achalasic in nNOS(−/−) and hypotensive in W/W(v) mutant mice. Gastroenterology 2001; 121: 34-42.
Kurahashi M, Niwa Y, Cheng J et al. Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut. Neurogastroenterol Motil 2008; 20: 521-31.
Iino S, Horiguchi K, Horiguchi S, Nojyo Y. c-Kit-negative fibroblast-like cells express platelet-derived growth factor receptor alpha in the murine gastrointestinal musculature. Histochem Cell Biol 2009; 131: 691-702.
Klemm MF, Lang RJ. Distribution of Ca2+-activated K+ channel (SK2 and SK3) immunoreactivity in intestinal smooth muscles of the guinea-pig. Clin Exp Pharmacol Physiol 2002; 29: 18-25.
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11600437 - Am J Physiol Cell Physiol. 2001 Nov;281(5):C1727-33
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9679037 - Gastroenterology. 1998 Aug;115(2):314-29
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7103120 - Anat Rec. 1982 May;203(1):129-46
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18194151 - Neurogastroenterol Motil. 2008 May;20(5):521-31
16166342 - Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G394-403
References_xml – reference: Kashyap P, Farrugia G. Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years. Gut 2010; 59: 1716-26.
– reference: Rumessen JJ, Thuneberg L, Mikkelsen HB. Plexus muscularis profundus and associated interstitial cells. II. Ultrastructural studies of mouse small intestine. Anat Rec 1982; 203: 129-46.
– reference: Fujita A, Takeuchi T, Jun H, Hata F. Localization of Ca2+-activated K+ channel, SK3, in fibroblast-like cells forming gap junctions with smooth muscle cells in the mouse small intestine. J Pharmacol Sci 2003; 92: 35-42.
– reference: Cobine CA, Hennig GW, Kurahashi M, Sanders KM, Ward SM, Keef KD. Relationship between interstitial cells of Cajal, fibroblast-like cells and inhibitory motor nerves in the internal anal sphincter. Cell Tissue Res 2011; 344: 17-30.
– reference: Ro S, Hatton WJ, Koh SD, Horowitz B. Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle. Am J Physiol Gastrointest Liver Physiol 2001; 281: G964-73.
– reference: Ueno T, Duenes JA, Zarroug AE, Sarr MG. Nitrergic mechanisms mediating inhibitory control of longitudinal smooth muscle contraction in mouse small intestine. J Gastrointest Surg 2004; 8: 831-41.
– reference: Vanderwinden JM, Rumessen JJ, De Laet MH, Vanderhaeghen JJ, Schiffmann SN. CD34+ cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal. Lab Invest 1999; 79: 59-65.
– reference: Vanderwinden JM, Rumessen JJ, de Kerchove d'Exaerde A Jr et al. Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease. Cell Tissue Res 2002; 310: 349-58.
– reference: Kurahashi M, Niwa Y, Cheng J et al. Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut. Neurogastroenterol Motil 2008; 20: 521-31.
– reference: Hoch RV, Soriano P. Roles of PDGF in animal development. Development 2003; 130: 4769-84.
– reference: Groneberg D, Konig P, Koesling D, Friebe A. Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle. Gastroenterology 2011; 140: 1608-17.
– reference: Vittal H, Farrugia G, Gomez G, Pasricha PJ. Mechanisms of disease: the pathological basis of gastroparesis--a review of experimental and clinical studies. Nat Clin Pract Gastroenterol Hepatol 2007; 4: 336-46.
– reference: Streutker CJ, Huizinga JD, Campbell F, Ho J, Riddell RH. Loss of CD117 (c-kit)- and CD34-positive ICC and associated CD34-positive fibroblasts defines a subpopulation of chronic intestinal pseudo-obstruction. Am J Surg Pathol 2003; 27: 228-35.
– reference: Spencer NJ, Hennig GW, Smith TK. Stretch-activated neuronal pathways to longitudinal and circular muscle in guinea pig distal colon. Am J Physiol Gastrointest Liver Physiol 2003; 284: G231-41.
– reference: Sivarao DV, Mashimo HL, Thatte HS, Goyal RK. Lower esophageal sphincter is achalasic in nNOS(−/−) and hypotensive in W/W(v) mutant mice. Gastroenterology 2001; 121: 34-42.
– reference: Choi KM, Gibbons SJ, Roeder JL et al. Regulation of interstitial cells of Cajal in the mouse gastric body by neuronal nitric oxide. Neurogastroenterol Motil 2007; 19: 585-95.
– reference: Zhang Y, Carmichael SA, Wang XY, Huizinga JD, Paterson WG. Neurotransmission in lower esophageal sphincter of W/Wv mutant mice. Am J Physiol Gastrointest Liver Physiol 2010; 298: G14-24.
– reference: Hosseini R, Benton DC, Dunn PM, Jenkinson DH, Moss GW. SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones. J Physiol 2001; 535: 323-34.
– reference: Ward SM, Morris G, Reese L, Wang XY, Sanders KM. Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters. Gastroenterology 1998; 115: 314-29.
– reference: Farrugia G. Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil 2008; 20(Suppl. 1): 54-63.
– reference: Karlsson L, Lindahl P, Heath JK, Betsholtz C. Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 2000; 127: 3457-66.
– reference: Faussone-Pellegrini MS, Grover M, Pasricha P et al. Ultrastructural differences between diabetic and idiopathic gastroparesis: The NIDDK gastroparesis clinical research consortium (GpCRC). J Cell Mol Med 2011; doi: 10.1111/j.1582-4934.2011.01451.x.
– reference: Iino S, Horiguchi K, Nojyo Y. Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide-sensitive guanylate cyclase in the guinea-pig gastrointestinal tract. Neuroscience 2008; 152: 437-48.
– reference: Grover M, Farrugia G, Lurken MS et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology 2011; 140: 1575-85. e8.
– reference: Bond CT, Sprengel R, Bissonnette JM et al. Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. Science 2000; 289: 1942-6.
– reference: Vanderwinden JM, Rumessen JJ, De Laet MH, Vanderhaeghen JJ, Schiffmann SN. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract. Cell Tissue Res 2000; 302: 145-53.
– reference: Kurahashi M, Zheng H, Dwyer L, Ward SM, Don Koh S, Sanders KM. A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles. J Physiol 2011; 589: 697-710.
– reference: El-Yazbi AF, Cho WJ, Boddy G, Schulz R, Daniel EE. Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles. Am J Physiol Gastrointest Liver Physiol 2006; 290: G394-403.
– reference: Rumessen JJ, Thuneberg L. Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers. Gastroenterology 1991; 100: 1417-31.
– reference: Horiguchi K, Komuro T. Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine. J Auton Nerv Syst 2000; 80: 142-7.
– reference: Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev 2008; 22: 1276-312.
– reference: Klemm MF, Lang RJ. Distribution of Ca2+-activated K+ channel (SK2 and SK3) immunoreactivity in intestinal smooth muscles of the guinea-pig. Clin Exp Pharmacol Physiol 2002; 29: 18-25.
– reference: Grunnet M, Jespersen T, Angelo K et al. Pharmacological modulation of SK3 channels. Neuropharmacology 2001; 40: 879-87.
– reference: Fujita A, Takeuchi T, Saitoh N, Hanai J, Hata F. Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract. Am J Physiol Cell Physiol 2001; 281: C1727-33.
– reference: Iino S, Horiguchi K, Horiguchi S, Nojyo Y. c-Kit-negative fibroblast-like cells express platelet-derived growth factor receptor alpha in the murine gastrointestinal musculature. Histochem Cell Biol 2009; 131: 691-702.
– reference: Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 1996; 93: 12008-13.
– reference: Iino S, Nojyo Y. Immunohistochemical demonstration of c-Kit-negative fibroblast-like cells in murine gastrointestinal musculature. Arch Histol Cytol 2009; 72: 107-15.
– volume: 281
  start-page: G964
  year: 2001
  end-page: 73
  article-title: Molecular properties of small‐conductance Ca2+‐activated K+ channels expressed in murine colonic smooth muscle
  publication-title: Am J Physiol Gastrointest Liver Physiol
– year: 2011
  article-title: Ultrastructural differences between diabetic and idiopathic gastroparesis: The NIDDK gastroparesis clinical research consortium (GpCRC)
  publication-title: J Cell Mol Med
– volume: 281
  start-page: C1727
  year: 2001
  end-page: 33
  article-title: Expression of Ca(2+)‐activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract
  publication-title: Am J Physiol Cell Physiol
– volume: 152
  start-page: 437
  year: 2008
  end-page: 48
  article-title: Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide‐sensitive guanylate cyclase in the guinea‐pig gastrointestinal tract
  publication-title: Neuroscience
– volume: 22
  start-page: 1276
  year: 2008
  end-page: 312
  article-title: Role of platelet‐derived growth factors in physiology and medicine
  publication-title: Genes Dev
– volume: 344
  start-page: 17
  year: 2011
  end-page: 30
  article-title: Relationship between interstitial cells of Cajal, fibroblast‐like cells and inhibitory motor nerves in the internal anal sphincter
  publication-title: Cell Tissue Res
– volume: 29
  start-page: 18
  year: 2002
  end-page: 25
  article-title: Distribution of Ca2+‐activated K+ channel (SK2 and SK3) immunoreactivity in intestinal smooth muscles of the guinea‐pig
  publication-title: Clin Exp Pharmacol Physiol
– volume: 589
  start-page: 697
  year: 2011
  end-page: 710
  article-title: A functional role for the ‘fibroblast‐like cells’ in gastrointestinal smooth muscles
  publication-title: J Physiol
– volume: 298
  start-page: G14
  year: 2010
  end-page: 24
  article-title: Neurotransmission in lower esophageal sphincter of W/W mutant mice
  publication-title: Am J Physiol Gastrointest Liver Physiol
– volume: 115
  start-page: 314
  year: 1998
  end-page: 29
  article-title: Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters
  publication-title: Gastroenterology
– volume: 310
  start-page: 349
  year: 2002
  end-page: 58
  article-title: Kit‐negative fibroblast‐like cells expressing SK3, a Ca2+‐activated K+ channel, in the gut musculature in health and disease
  publication-title: Cell Tissue Res
– volume: 302
  start-page: 145
  year: 2000
  end-page: 53
  article-title: CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract
  publication-title: Cell Tissue Res
– volume: 40
  start-page: 879
  year: 2001
  end-page: 87
  article-title: Pharmacological modulation of SK3 channels
  publication-title: Neuropharmacology
– volume: 290
  start-page: G394
  year: 2006
  end-page: 403
  article-title: Impact of caveolin‐1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles
  publication-title: Am J Physiol Gastrointest Liver Physiol
– volume: 140
  start-page: 1575
  year: 2011
  end-page: 85
  article-title: Cellular changes in diabetic and idiopathic gastroparesis
  publication-title: Gastroenterology
– volume: 27
  start-page: 228
  year: 2003
  end-page: 35
  article-title: Loss of CD117 (c‐kit)‐ and CD34‐positive ICC and associated CD34‐positive fibroblasts defines a subpopulation of chronic intestinal pseudo‐obstruction
  publication-title: Am J Surg Pathol
– volume: 127
  start-page: 3457
  year: 2000
  end-page: 66
  article-title: Abnormal gastrointestinal development in PDGF‐A and PDGFR‐(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis
  publication-title: Development
– volume: 535
  start-page: 323
  year: 2001
  end-page: 34
  article-title: SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones
  publication-title: J Physiol
– volume: 19
  start-page: 585
  year: 2007
  end-page: 95
  article-title: Regulation of interstitial cells of Cajal in the mouse gastric body by neuronal nitric oxide
  publication-title: Neurogastroenterol Motil
– volume: 121
  start-page: 34
  year: 2001
  end-page: 42
  article-title: Lower esophageal sphincter is achalasic in nNOS(−/−) and hypotensive in W/W mutant mice
  publication-title: Gastroenterology
– volume: 59
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Snippet Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are...
Background  Emerging evidence suggests that “fibroblast‐like cells” (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are...
Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are...
Background Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are...
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wiley
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StartPage 844
SubjectTerms Adult
Antibodies
Biopsy
Case-Control Studies
Cell body
Cytology
Diabetes Complications - metabolism
Diabetes mellitus
Enteric nervous system
Female
fibroblast-like cells
Ganglia
Gastric Emptying
gastroparesis
Gastroparesis - metabolism
Humans
Immunohistochemistry
Interstitial cells
interstitial cells of Cajal
Male
Muscle, Smooth - cytology
Muscle, Smooth - metabolism
myenteric plexus
Myenteric Plexus - metabolism
Nervous system
platelet-derived growth factor receptor
Platelet-derived growth factor receptors
Potassium channels (calcium-gated)
Receptor, Platelet-Derived Growth Factor alpha - metabolism
Small-Conductance Calcium-Activated Potassium Channels - metabolism
Smooth muscle
Stomach - cytology
Stomach - metabolism
Title Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans
URI https://api.istex.fr/ark:/67375/WNG-N4B5KP1N-V/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1365-2982.2012.01944.x
https://www.ncbi.nlm.nih.gov/pubmed/22650155
https://www.proquest.com/docview/1034796495
https://www.proquest.com/docview/1038599341
https://pubmed.ncbi.nlm.nih.gov/PMC3756591
Volume 24
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