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

World J Gastroenterol. 2009 Mar 28;15(12):1431-42. doi: 10.3748/wjg.15.1431.


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.

MeSH terms

  • Actins / drug effects
  • Actins / genetics
  • Actins / metabolism
  • Alternative Splicing
  • Biopsy
  • Cell Differentiation / drug effects*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Colon / cytology*
  • Colon / drug effects
  • Colon / pathology
  • Colon / physiology*
  • Colonoscopy
  • Colorectal Neoplasms / surgery
  • Culture Media, Conditioned
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Transforming Growth Factor beta1 / pharmacology*


  • Actins
  • Culture Media, Conditioned
  • RNA, Messenger
  • Transforming Growth Factor beta1