Fibroblast growth factors modulate intestinal epithelial cell growth and migration

Abstract

Background/aims: Various peptide growth factors have been found to exert functional effects among epithelial cell populations. This study assessed the role of certain fibroblast growth factors (FGFs) (acidic FGF, basic FGF, and keratinocyte growth factor) in the regulation of intestinal epithelial cell proliferation and restitution.

Methods: Recombinant growth factors were added to subconfluent cultures of IEC-6, Caco-2, and HT-29 cell lines with subsequent assessment of [3H]-thymidine incorporation. The effects on an in vitro model of restitution were assessed by quantitation of cells migrating into standard wounds established in confluent monolayers of IEC-6 cells. Transforming growth factor beta (TGF-beta) content of growth factor-treated wounded monolayers was assessed by Northern blot and bioassay.

Results: Acidic FGF, basic FGF, and keratinocyte growth factor caused a modest increase in proliferation of IEC-6, Caco-2, and HT-29 cell lines. Acidic FGF and basic FGF promoted intestinal epithelial cell restitution in vitro up to 10-fold, in conjunction with the enhanced expression of TGF-beta messenger RNA and protein. Promotion of IEC-6 restitution by acidic and basic FGF could be blocked by addition of immunoneutralizing anti-TGF-beta antisera.

Conclusions: FGFs that exert effects on fibroblast cells also exert effects on intestinal epithelial cell populations and may help promote epithelial cell restitution, the initial step of intestinal wound healing through a TGF-beta-dependent pathway.