Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis
We recently observed reduced autophagy in Crohn’s disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn’s di...
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| Published in | Cells (Basel, Switzerland) Vol. 8; no. 9; p. 1078 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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13.09.2019
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| Abstract | We recently observed reduced autophagy in Crohn’s disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn’s disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis. |
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| AbstractList | We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis. We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis.We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis. |
| Author | Gisbert-Ferrándiz, Laura Canet, Francisco Esplugues, Juan V. Macias-Ceja, Dulce C. Calatayud, Sara Alós, Rafael Navarro, Francisco Cosin-Roger, Jesus Ortiz-Masiá, Dolores Barrachina, María D. |
| AuthorAffiliation | 2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 46010 Valencia, Spain 4 Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain 3 Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain 5 Departamento de Cirugía del Aparato Digestivo, Hospital La Fe, 46526 Valencia, Spain 6 Departamento de Cirugía y Coloproctología, Hospital de Manises, 46940 Valencia, Spain 1 Hospital Dr Peset, FISABIO, 46017 Valencia, Spain |
| AuthorAffiliation_xml | – name: 5 Departamento de Cirugía del Aparato Digestivo, Hospital La Fe, 46526 Valencia, Spain – name: 3 Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain – name: 2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 46010 Valencia, Spain – name: 4 Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain – name: 1 Hospital Dr Peset, FISABIO, 46017 Valencia, Spain – name: 6 Departamento de Cirugía y Coloproctología, Hospital de Manises, 46940 Valencia, Spain |
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| SubjectTerms | Animal models Animals Autophagy Autophagy - drug effects Brief Report Colitis Collagen Collagen - metabolism Colon Crohn Disease - complications Crohn's disease Cytokines Disease Models, Animal Fibroblasts Fibroblasts - metabolism Fibroblasts - pathology Fibrosis Fibrosis - drug therapy Gene expression Immunosuppressive Agents - pharmacology Inflammation Inflammation - drug therapy Inflammation - immunology Inflammatory bowel diseases intestinal fibrosis Intestine Intestines - pathology Mice Mice, Inbred C57BL Phagocytosis Proteins Sirolimus - pharmacology Software Variance analysis |
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| Title | Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis |
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