Brenmoehl J, Miller SN, Hofmann C, Vogl D, Falk W, Schölmerich J, Rogler G. Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration. World J Gastroenterol 2009; 15(12): 1431-1442 [PMID: 19322915 DOI: 10.3748/wjg.15.1431]
Corresponding Author of This Article
Julia Brenmoehl, PhD, Department of Internal Medicine II, University of Jena, Jena 07747, Germany. julia.brenmoehl@med.uni-jena.de
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World J Gastroenterol. Mar 28, 2009; 15(12): 1431-1442 Published online Mar 28, 2009. doi: 10.3748/wjg.15.1431
Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration
Julia Brenmoehl, Sandra Nicole Miller, Claudia Hofmann, Daniela Vogl, Werner Falk, Jürgen Schölmerich, Gerhard Rogler
Julia Brenmoehl, Sandra Nicole Miller, Claudia Hofmann, Daniela Vogl, Werner Falk, Jürgen Schölmerich, Gerhard Rogler, Department of Internal Medicine I, University of Regensburg, 93055 Regensburg, Germany
Julia Brenmoehl, Department of Internal Medicine II, University of Jena, 07747 Jena, Germany
Gerhard Rogler, Clinic of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zurich, 8091 Zurich, Switzerland
Author contributions: Brenmoehl J performed the quantitative mRNA analyses (Taqman-PCR) and western blotting of fibronectin and the fibronectin isoforms, and wrote the manuscript; Miller SN performed the migration assays, western blotting and staining of a-smooth muscle actin, and wrote the manuscript; Hofmann C performed the western blotting of phosphorylated and total focal adhesion kinase and wrote the manuscript; Vogl D contributed to biopsies collection, data collection and isolation of colonic lamina propria fibroblasts; Falk W contributed to data interpretation and to writing the manuscript; Schölmerich J contributed to the overall interpretation of data and writing of the manuscript; Rogler G planned and co-ordinated the study and wrote the manuscript.
Correspondence to: Julia Brenmoehl, PhD, Department of Internal Medicine II, University of Jena, Jena 07747, Germany. julia.brenmoehl@med.uni-jena.de
Telephone: +49-3641-9324227
Fax: +49-3641-9325827
Received: May 24, 2008 Revised: October 15, 2008 Accepted: October 22, 2008 Published online: March 28, 2009
Abstract
AIM: To investigate the effects of transforming growth factor β1 (TGF-β1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro.
METHODS: Primary CLPF cultures were incubated with TGF-β1 and analyzed for production of α-smooth muscle actin (α-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-β1 for 2 d did not change α-SMA levels, while TGF-β1 treatment for 6 d significantly increased α-SMA production. Short term incubation (6 h) with TGF-β1 enhanced CLPF migration, while long term treatment (6 d) of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 (2 d) in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-β1-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-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact (6 h) of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production.
