Fibroblast growth factors modulate intestinal epithelial cell growth and migration.
OBJECTIVE
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.
Dignass
A U
AU
Department of Medicine, Massachusetts General Hospital, Boston.
Tsunekawa
S
S
Podolsky
D K
DK
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000737:chemistry / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014945:Wound Healing
C496453:FGF7 protein, human; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors