Migration of colonic lamina propria fibroblasts (CLPF) plays an important role during the progression of fibrosis and fistulae in Crohn's disease. Transforming growth factor- beta (TGF- beta) is involved in the regulation of cell migration, cell differentiation, extracellular matrix deposition, and immune responses. Since the regulation of migration and differentiation of intestinal fibroblasts is an important mechanism during intestinal wound healing and fibrosis, it is important to investigate the effect of TGF- beta 1 on these processes and on fibronectin (FN) and FN isoform production
A research team led by Dr. Julia Brenmoehl from University of Jena addressed this issue and their study will be published on March 28, 2009 in the World Journal of Gastroenterology.
In their study, primary CLPF cultures were incubated with TGF-beta 1 and analyzed for production of alpha-smooth muscle actin (alpha-SMA), 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.
They found that incubation of CLPF with TGF-beta 1 for 2 days did not change alpha-SMA levels, while TGF-beta 1 treatment for 6 day significantly increased alpha-SMA production. Short term incubation (6 hours) with TGF-beta 1 enhanced CLPF migration, while long term treatment (6 day) 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 days) in contrast to long term incubation with TGF-beta 1 for 6 days. 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.
Their results indicated 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 hours) of fibroblasts with TGF-beta 1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of alpha-SMA production. This study adds to the understanding of the role of TGF- beta in intestinal wound healing and stricture formation.
Reference: Brenmoehl J, Miller SN, Hofmann C, Vogl D, Falk W, Schölmerich J, Rogler G. Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates
their migration. World J Gastroenterol 2009; 15(12): 1431-1442
http://www.wjgnet.com/1007-9327/15/1431.asp
Correspondence to: 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 Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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World Journal of Gastroenterology