Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway
Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in...
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| Published in | Cellular physiology and biochemistry Vol. 51; no. 5; pp. 2030 - 2040 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel, Switzerland
S. Karger AG
01.12.2018
Cell Physiol Biochem Press GmbH & Co KG |
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| Abstract | Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. Methods: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). Results: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn’t show significant difference between PE and normal placentas. Conclusion: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis. |
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| AbstractList | Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion.
LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP).
LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas.
LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis. Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion.BACKGROUND/AIMSPreeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion.LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP).METHODSLN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP).LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas.RESULTSLN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas.LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.CONCLUSIONLN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis. Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. Methods: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). Results: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn’t show significant difference between PE and normal placentas. Conclusion: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis. |
| Author | Shan, Nan Li, Hai Ying Xiong, Xi Liu, Ya Ming Li, Qin Huang, Shuai Zhang, Xue Mei Tong, Chao Baker, Phillip Li, Qing Shu Qi, Hong Bo |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30522103$$D View this record in MEDLINE/PubMed |
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| Keywords | Laminin (LN)- α5 Trophoblast PI3K signaling pathway Preeclampsia |
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| References | Gao L, Qi HB, Kamana KC, Zhang XM, Zhang H, Baker PN: Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia. J Hypertens 2015; 33: 106-117. Yang Z, Bai B, Luo X, Xiao X, Liu X, Ding Y, Zhang H, Gao L, Li J, Qi H: Downregulated Krüppel-like factor 8 is involved in decreased trophoblast invasion under hypoxia-reoxygenation conditions. Reprod Sci 2014; 21: 72-81. Hung TH, Chen SF, Li MJ, Yeh YL, Hsieh TT: Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation. PLoS One 2010; 5:e12202. Fisher SJ: Why is placentation abnormal in preeclampsia. Am J Obstet Gynecol 2015; 213:S115-122. Li E, Zhang Y: DNA Methylation in Mammals. Cold Spring Harb Perspect Biol 2014; 6:a019133. Pozzi A, Yurchenco PD, Lozzo RV: The nature and biology of basement membranes. Matrix Biol 2017; 57-58: 1–11. Frantz C, Stewart KM, Weaver VM: The extracellular matrix at a glance. J Cell Sci 2010; 123: 4195–4200. Ritié L, Spenlé C, Lacroute J, Bolcato-Bellemin AL, Lefebvre O, Bole-Feysot C, Jost B, Klein A, Arnold C, Kedinger M, Bagnard D, Orend G, Simon-Assmann P: Abnormal Wnt and PI3Kinase signaling in the malformed intestine of LN-a5 deficient mice. PLoS One 2012; 7:e37710. Furuhashi N, Kimura H, Nagae H, Yajima A, Kimura C, Saito T: Serum laminin levels in normal pregnancy and preeclampsia. Gynecol Obstet Invest 1993; 36: 172-175. Mukhopadhyay A, Ravikumar G, Meraaj H, Dwarkanath P, Thomas A, Crasta J, Thomas T, Kurpad AV, Sridhar TS: Placental expression of DNA methyltransferase 1 (DNMT1): Gender-specific relation with human placental growth. Placenta 2016; 48: 119-125. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L: Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014; 2:e323-333. Shan N, Zhang X, Xiao X, Zhang H, Tong C, Luo X, Chen Y, Liu X, Yin N, Deng Q, Qi H: Laminin a4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas. Placenta 2015; 36: 809-820. Liao Z, Nan G, Yan Z, Zeng L, Deng Y, Ye J, Zhang Z, Qiao M, Li R, Denduluri S, Wang J, Wei Q, Geng N, Zhao L, Lu S, Wang X, Zhou G, Luu HH, Haydon RC, He TC1, Wang Z: The Anthelmintic Drug Niclosamide Inhibits the Proliferative Activity of Human Osteosarcoma Cells by Targeting Multiple Signal Pathways. Curr Cancer Drug Targets 2015; 15: 726-738. Simonova OA, Kuznetsova EB, Poddubskaya EV, Kekeeva TV, Kerimov RA, Trotsenko ID, Tanas AS, Rudenko VV, Alekseeva EA, Zaletayev DV, Strelnikov VV: DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues. Mol Biol (Mosk) 2015; 49: 598-607. Bonnans C, Chou J, Werb Z: Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014; 15: 786–801. Paridaens H, Gruson D: Pre-eclampsia: overview on the role of biomarkers in 2016. Ann Biol Clin (Paris) 2017; 75: 245-258. Guo X, Jing C, Li L, Zhang L, Shi Y, Wang J, Liu J, Li C: Down-regulation of VEZT gene expression in human gastric cancer involves promoter methylation and miR-43c. Biochem Biophys Res Commun 2011; 404: 622-627. Kühnel E, Kleff V, Stojanovska V, Kaiser S, Waldschütz R, Herse F, Plösch T, Winterhager E, Gellhaus A: Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model. J Cell Biochem 2017; 118: 1316-1329. Durbeej M: Laminins. Cell Tissue Res 2010; 339: 259-268. Algharabil J, Kintner DB, Wang Q, Begum G, Clark PA, Yang SS, Lin SH, Kahle KT, Kuo JS, Sun D: Inhibition of Na(+)-K(+)-2Cl(-) cotransporter isoform 1 accelerates temozolomide-mediated apoptosis in glioblastoma cancer cells. Cell Physiol Biochem 2012; 30: 33-48. Soares MJ, Chakraborty D, Renaud SJ, Kubota K, Bu P, Konno T, Rumi MA: Regulatory pathways controlling the endovascular invasive trophoblast cell lineage. J Reprod Dev 2012; 58: 283-287. Domogatskaya A, Rodin S, Tryggvason K: Functional diversity of laminins. Annu Rev Cell Dev Biol 2012; 28: 523-553. Jia Y, Li T, Huang X, Xu X, Zhou X, Jia L, Zhu J, Xie D, Wang K, Zhou Q, Jin L, Zhang J, Duan T: Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia. Hypertension 2017; 69: 356-366. Takáč T, Pechan T, Samajová O, Samaj J: Vesicular trafficking and stress response coupled to PI3K inhibition by LY294002 as revealed by proteomic and cell biological analysis. J Proteome Res 2013; 12: 4435-4448. Savino W, Mendes-da-Cruz DA, Golbert DC, Riederer I, Cotta-de-Almeida V: Laminin-Mediated Interactions in Thymocyte Migration and Development. Front Immunol 2015; 6: 579. Miner JH, Cunningham J, Sanes JR: Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 1998; 143: 1713-1723. Hynes RO: The evolution of metazoan extracellular matrix. J Cell Biol 2012; 196: 671-679. Pulido D, Briggs DC, Hua J, Hohenester E: Crystallographic analysis of the laminin β2 short arm reveals how the LF domain is inserted into a regular array of LE domains. Matrix Biol 2017; 57-58: 204-212. Kikkawa Y, Miner JH: Molecular dissection of laminin alpha 5 in vivo reveals separable domain-specific roles in embryonic development and kidney function. Dev Biol 2006; 296: 265-277. Lin C, Werner R, Ma L, Miner JH: Requirement for basement membrane laminin α5 during urethral and external genital development. Mech Dev 2016; 141: 62-69. Shen Z, Wu Y, Chen X, Chang X, Zhou Q, Zhou J, Ying H, Zheng J, Duan T, Wang K: Decreased maternal serum 2-methoxyestradiol levels are associated with the development of preeclampsia. Cell Physiol Biochem 2014; 34: 2189-2199. Simone Sampalolo, Filomena Napolitano, Alfonsina Tirozzi, Mafalda Giovanna Reccia, Luca Lombardi, Olipia Farina, Adriano Barra, Ferdinando Cirillo, Mariarosa Anna Beatrice Melone, Fernando Gianfrancesco, Giuseppe Di lorio, Teresa Esposito: Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix. J Med Genet 2017; 54: 710-720. Jia RZ, Ding GC, Gu CM, Huang T, Rui C, Wang YX, Lu Q: CDX2 enhances HTR-8/SVneo trophoblast cell invasion by altering the expression of matrix metalloproteinases. Cell Physiol Biochem 2014; 34: 628-636. Wiradjaja, F, DiTommaso T, Smyth I: Basement Membranes in Development and Disease. Birth Defects Res C Embryo Today 2010; 90: 8-31. Miner JH: Laminins and their roles in mammals. Microsc Res Tech 2008; 71: 349-356. Spenlé C, Simon-Assmann P, Orend G, Miner JH: Laminin α5 guides tissue patterning and organogenesis. Cell Adh Migr 2013; 7: 90-100. Engelman JA., Luo J, Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nature reviews Genetics 2006; 7: 606-619. Gao J, DeRouen MC, Chen CH, Nguyen M, Nguyen NT, Ido H, Harada K, Sekiguchi K, Morgan BA, Miner JH, Oro AE, Marinkovich MP: Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. Genes Dev 2008; 22: 2111-2124. Branco MR, King M, Perez-Garcia V, Bogutz AB, Caley M, Fineberg E, Lefebvre L, Cook SJ, Dean W, Hemberger M, Reik W: Maternal DNA Methylation Regulates Early Trophoblast Development. Dev Cell 2015; 36: 152-163. Cotton AM, Avila L, Penaherrera MS, Affleck JG, Robinson WP, Brown CJ : Inactive X chromosome-specific reduction in placental DNA methylation. Hum Mol Genet 2009; 18: 3544-3552. Gopal SK, Greening DW, Zhu HJ, Simpson RJ, Mathias RA: Transformed MDCK cells secrete elevated MMP1 that generates LN-A5 fragments promoting endothelial cell angiogenesis. Sci Rep 2016; 6: 28321. |
| References_xml | – reference: Durbeej M: Laminins. Cell Tissue Res 2010; 339: 259-268. – reference: Algharabil J, Kintner DB, Wang Q, Begum G, Clark PA, Yang SS, Lin SH, Kahle KT, Kuo JS, Sun D: Inhibition of Na(+)-K(+)-2Cl(-) cotransporter isoform 1 accelerates temozolomide-mediated apoptosis in glioblastoma cancer cells. Cell Physiol Biochem 2012; 30: 33-48. – reference: Simonova OA, Kuznetsova EB, Poddubskaya EV, Kekeeva TV, Kerimov RA, Trotsenko ID, Tanas AS, Rudenko VV, Alekseeva EA, Zaletayev DV, Strelnikov VV: DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues. Mol Biol (Mosk) 2015; 49: 598-607. – reference: Hung TH, Chen SF, Li MJ, Yeh YL, Hsieh TT: Differential effects of concomitant use of vitamins C and E on trophoblast apoptosis and autophagy between normoxia and hypoxia-reoxygenation. PLoS One 2010; 5:e12202. – reference: Kikkawa Y, Miner JH: Molecular dissection of laminin alpha 5 in vivo reveals separable domain-specific roles in embryonic development and kidney function. Dev Biol 2006; 296: 265-277. – reference: Savino W, Mendes-da-Cruz DA, Golbert DC, Riederer I, Cotta-de-Almeida V: Laminin-Mediated Interactions in Thymocyte Migration and Development. Front Immunol 2015; 6: 579. – reference: Wiradjaja, F, DiTommaso T, Smyth I: Basement Membranes in Development and Disease. Birth Defects Res C Embryo Today 2010; 90: 8-31. – reference: Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L: Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014; 2:e323-333. – reference: Domogatskaya A, Rodin S, Tryggvason K: Functional diversity of laminins. Annu Rev Cell Dev Biol 2012; 28: 523-553. – reference: Gao L, Qi HB, Kamana KC, Zhang XM, Zhang H, Baker PN: Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia. J Hypertens 2015; 33: 106-117. – reference: Jia Y, Li T, Huang X, Xu X, Zhou X, Jia L, Zhu J, Xie D, Wang K, Zhou Q, Jin L, Zhang J, Duan T: Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia. Hypertension 2017; 69: 356-366. – reference: Miner JH: Laminins and their roles in mammals. Microsc Res Tech 2008; 71: 349-356. – reference: Spenlé C, Simon-Assmann P, Orend G, Miner JH: Laminin α5 guides tissue patterning and organogenesis. Cell Adh Migr 2013; 7: 90-100. – reference: Cotton AM, Avila L, Penaherrera MS, Affleck JG, Robinson WP, Brown CJ : Inactive X chromosome-specific reduction in placental DNA methylation. Hum Mol Genet 2009; 18: 3544-3552. – reference: Liao Z, Nan G, Yan Z, Zeng L, Deng Y, Ye J, Zhang Z, Qiao M, Li R, Denduluri S, Wang J, Wei Q, Geng N, Zhao L, Lu S, Wang X, Zhou G, Luu HH, Haydon RC, He TC1, Wang Z: The Anthelmintic Drug Niclosamide Inhibits the Proliferative Activity of Human Osteosarcoma Cells by Targeting Multiple Signal Pathways. Curr Cancer Drug Targets 2015; 15: 726-738. – reference: Furuhashi N, Kimura H, Nagae H, Yajima A, Kimura C, Saito T: Serum laminin levels in normal pregnancy and preeclampsia. Gynecol Obstet Invest 1993; 36: 172-175. – reference: Branco MR, King M, Perez-Garcia V, Bogutz AB, Caley M, Fineberg E, Lefebvre L, Cook SJ, Dean W, Hemberger M, Reik W: Maternal DNA Methylation Regulates Early Trophoblast Development. Dev Cell 2015; 36: 152-163. – reference: Bonnans C, Chou J, Werb Z: Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014; 15: 786–801. – reference: Fisher SJ: Why is placentation abnormal in preeclampsia. Am J Obstet Gynecol 2015; 213:S115-122. – reference: Mukhopadhyay A, Ravikumar G, Meraaj H, Dwarkanath P, Thomas A, Crasta J, Thomas T, Kurpad AV, Sridhar TS: Placental expression of DNA methyltransferase 1 (DNMT1): Gender-specific relation with human placental growth. Placenta 2016; 48: 119-125. – reference: Paridaens H, Gruson D: Pre-eclampsia: overview on the role of biomarkers in 2016. Ann Biol Clin (Paris) 2017; 75: 245-258. – reference: Soares MJ, Chakraborty D, Renaud SJ, Kubota K, Bu P, Konno T, Rumi MA: Regulatory pathways controlling the endovascular invasive trophoblast cell lineage. J Reprod Dev 2012; 58: 283-287. – reference: Lin C, Werner R, Ma L, Miner JH: Requirement for basement membrane laminin α5 during urethral and external genital development. Mech Dev 2016; 141: 62-69. – reference: Li E, Zhang Y: DNA Methylation in Mammals. Cold Spring Harb Perspect Biol 2014; 6:a019133. – reference: Kühnel E, Kleff V, Stojanovska V, Kaiser S, Waldschütz R, Herse F, Plösch T, Winterhager E, Gellhaus A: Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model. J Cell Biochem 2017; 118: 1316-1329. – reference: Jia RZ, Ding GC, Gu CM, Huang T, Rui C, Wang YX, Lu Q: CDX2 enhances HTR-8/SVneo trophoblast cell invasion by altering the expression of matrix metalloproteinases. Cell Physiol Biochem 2014; 34: 628-636. – reference: Yang Z, Bai B, Luo X, Xiao X, Liu X, Ding Y, Zhang H, Gao L, Li J, Qi H: Downregulated Krüppel-like factor 8 is involved in decreased trophoblast invasion under hypoxia-reoxygenation conditions. Reprod Sci 2014; 21: 72-81. – reference: Miner JH, Cunningham J, Sanes JR: Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 1998; 143: 1713-1723. – reference: Gopal SK, Greening DW, Zhu HJ, Simpson RJ, Mathias RA: Transformed MDCK cells secrete elevated MMP1 that generates LN-A5 fragments promoting endothelial cell angiogenesis. Sci Rep 2016; 6: 28321. – reference: Hynes RO: The evolution of metazoan extracellular matrix. J Cell Biol 2012; 196: 671-679. – reference: Ritié L, Spenlé C, Lacroute J, Bolcato-Bellemin AL, Lefebvre O, Bole-Feysot C, Jost B, Klein A, Arnold C, Kedinger M, Bagnard D, Orend G, Simon-Assmann P: Abnormal Wnt and PI3Kinase signaling in the malformed intestine of LN-a5 deficient mice. PLoS One 2012; 7:e37710. – reference: Frantz C, Stewart KM, Weaver VM: The extracellular matrix at a glance. J Cell Sci 2010; 123: 4195–4200. – reference: Takáč T, Pechan T, Samajová O, Samaj J: Vesicular trafficking and stress response coupled to PI3K inhibition by LY294002 as revealed by proteomic and cell biological analysis. J Proteome Res 2013; 12: 4435-4448. – reference: Pulido D, Briggs DC, Hua J, Hohenester E: Crystallographic analysis of the laminin β2 short arm reveals how the LF domain is inserted into a regular array of LE domains. Matrix Biol 2017; 57-58: 204-212. – reference: Simone Sampalolo, Filomena Napolitano, Alfonsina Tirozzi, Mafalda Giovanna Reccia, Luca Lombardi, Olipia Farina, Adriano Barra, Ferdinando Cirillo, Mariarosa Anna Beatrice Melone, Fernando Gianfrancesco, Giuseppe Di lorio, Teresa Esposito: Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix. J Med Genet 2017; 54: 710-720. – reference: Engelman JA., Luo J, Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nature reviews Genetics 2006; 7: 606-619. – reference: Pozzi A, Yurchenco PD, Lozzo RV: The nature and biology of basement membranes. Matrix Biol 2017; 57-58: 1–11. – reference: Shen Z, Wu Y, Chen X, Chang X, Zhou Q, Zhou J, Ying H, Zheng J, Duan T, Wang K: Decreased maternal serum 2-methoxyestradiol levels are associated with the development of preeclampsia. Cell Physiol Biochem 2014; 34: 2189-2199. – reference: Gao J, DeRouen MC, Chen CH, Nguyen M, Nguyen NT, Ido H, Harada K, Sekiguchi K, Morgan BA, Miner JH, Oro AE, Marinkovich MP: Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. Genes Dev 2008; 22: 2111-2124. – reference: Guo X, Jing C, Li L, Zhang L, Shi Y, Wang J, Liu J, Li C: Down-regulation of VEZT gene expression in human gastric cancer involves promoter methylation and miR-43c. Biochem Biophys Res Commun 2011; 404: 622-627. – reference: Shan N, Zhang X, Xiao X, Zhang H, Tong C, Luo X, Chen Y, Liu X, Yin N, Deng Q, Qi H: Laminin a4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas. Placenta 2015; 36: 809-820. |
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| Snippet | Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal... Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and... |
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| SubjectTerms | Angiogenesis Breast cancer Cell adhesion & migration Deoxyribonucleic acid DNA DNA methylation Extracellular matrix Hypertension Kinases Laminin (LN)- α5 Mammals Membranes Original Paper Pathogenesis PI3K signaling pathway Preeclampsia Pregnancy Proteins Roles Trophoblast |
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| Title | Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway |
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