Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates their migration

Brenmoehl, Julia and Miller, Sandra Nicole and Hofmann, Claudia and Vogl, Daniela and Falk, Werner and Schoelmerich, Juergen and Rogler, Gerhard (2009) Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates their migration. WORLD JOURNAL OF GASTROENTEROLOGY, 15 (12). pp. 1431-1442. ISSN 1007-9327,

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Abstract

AIM: To investigate the effects of transforming growth factor beta 1 (TGF-beta 1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro. METHODS: Primary CLPF cultures were incubated with TGF-beta 1 and analyzed for production of alpha-smooth muscle actin (alpha-SMA), fibronectin (FN) and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase (FAK) in CLPF were analyzed after induction of migration. RESULTS: Incubation of CLPF with TGF-beta 1 for 2 d did not change alpha-SMA levels, while TGF-beta 1 treatment for 6 d significantly increased alpha-SMA production. Short term incubation (6 h) with TGF-beta 1 enhanced CLPF migration, while long term treatment (6 d) of CLPF with TGF-beta 1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-beta 1 (2 d) in contrast to long term incubation with TGF-beta 1 for 6 d. After induction of migration, TGF-beta 1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells. CONCLUSION: Long term incubation of CLPF with TGF-beta 1 induced differentiation into myofibroblasts with enhanced alpha-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact (6 h) of fibroblasts with TGF-beta 1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of alpha-SMA production. (C) 2009 The WJG Press and Baishideng. All rights reserved.

Item Type: Article
Uncontrolled Keywords: GROWTH-FACTOR-BETA; FOCAL ADHESION KINASE; INFLAMMATORY-BOWEL-DISEASE; HUMAN LUNG FIBROBLASTS; CHEMOTACTIC MIGRATION; FIBRONECTIN; TGF-BETA-1; EXPRESSION; PROLIFERATION; ISOFORMS; Transforming growth factor beta 1; Colonic fibroblasts; Myofibroblasts; Migration; Fibronectin
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 21 Sep 2020 06:33
Last Modified: 21 Sep 2020 06:33
URI: https://pred.uni-regensburg.de/id/eprint/29255

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