Connective tissue growth factor in indomethacin-induced rat gastric ulcer.
The healing of gastric ulcers requires not only the complete epithelial covering but also the restitution of connective tissue. Transforming growth factor-beta (TGF-beta) and its downstream mediator, connective tissue growth factor (CTGF), are potent stimulators for connective tissue formation during wound healing. The expression of TGF-beta, CTGF and type III collagen mRNA in indomethacin-induced gastric ulcers in rat, was investigated by Northern blot analysis. We also examined the localization of CTGF producing cells by in situ hybridization. Northern blot analysis showed expression of TGF-beta mRNA on days 1 and 3 after indomethacin administration, expression of CTGF mRNA on days 1, 3 and 7 and type III collagen mRNA expression on days 1, 3, 7 and 12, respectively. Control animals showed no expression of TGF-beta, CTGF or type III collagen mRNA. In situ hybridization showed CTGF mRNA positive cells on days 1, 3 and 7 after ulcer induction in fibroblast-like cells and in some of the blood vessels. Thus our findings indicate that growth factor CTGF, together with TGF-beta, participates in gastric ulcer healing by regulating connective tissue formation and angiogenesis. These results are compatible with the role of CTGF as a downstream mediator of TGF-beta effects.
Lempinen
Marko
M
Fourth Department of Surgery, Helsinki University Central Hospital, Kasarmikatu 11-13, FIN-001 30 Helsinki, Finland. marko.lempinen@hus.fi
Inkinen
K
K
Wolff
H
H
Ahonen
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D024061:Collagen Type III / Q000235:genetics; D055513:Connective Tissue Growth Factor; D015870:Gene Expression; D017874:Immediate-Early Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D007213:Indomethacin / Q000633:toxicity*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; C526316:CCN2 protein, rat; D024061:Collagen Type III; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D007213:Indomethacin