Role of fibroblast growth factor-2 in the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human intestinal myofibroblasts.
OBJECTIVE
The coordinated expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) plays a crucial role in tissue remodeling. We investigated the effects of fibroblast growth factor (FGF)-2 on the secretion of MMPs and TIMPs in human intestinal subepithelial myofibroblasts (SEMFs).


METHODS
The secretion of MMP-s and TIMPs was determined by ELISA or Western blotting. The mRNA expression of MMPs and TIMPs was assessed by Northern blotting. The activating protein (AP)-1-DNA binding activity was evaluated by electrophoretic gel mobility shift assays (EMSA).


RESULTS
Unstimulated intestinal SEMFs constitutively secreted MMP-2 and TIMP-2. FGF-2 stimulated MMP-1, MMP-3 and TIMP-1 secretion, but did not affect MMP-2 or TIMP-2 secretion. FGF-2 induced AP-1-DNA binding activity, and the c-Jun/AP-1 inhibitor curcumin attenuated the FGF-2-induced MMP-1, -3 and TIMP-1 mRNA expression. Mitogen-activated protein (MAP) kinase inhibitors (U0126 and PD098059) also blocked the MMP-1, -3 and TIMP-1 secretion. Furthermore, FGF-2 dose-dependently induced FGF-2 mRNA expression in these cells.


CONCLUSIONS
FGF-2 may be one of important regulatory factors for extracellular matrix turnover via a modulation of MMP and TIMP secretion from SEMFs.
Yasui
Hirofumi
H
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan.
Andoh
Akira
A
Bamba
Shigeki
S
Inatomi
Osamu
O
Ishida
Hideaki
H
Fujiyama
Yoshihide
Y
D015153:Blotting, Western; D002450:Cell Communication; D018929:Cell Culture Techniques; D004064:Digestive System / Q000166:cytology* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000378:metabolism; D014945:Wound Healing
D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D012313:RNA; D020782:Matrix Metalloproteinases