Korean J Nephrol.  2004 Nov;23(6):888-897.

Effect of HGF on the Production of TGF-beta, Fibronectin, and Collagen Ia in the Murine Mesangial Cells

• An WS
• Bae HR
• Rha SH
• Kim SE
• Kim KH

Abstract

BACKGROUND
Hepatocyte growth factor (HGF) is a multifunctional protein especially implicated in tissue repair and regeneration. In a murine model of chronic glomerulonepritis, subcutaneous injection of recombinant HGF inhibited renal fibrosis. Although these favorable results were accompanied by decreased expression of TGF-beta in renal tissue, the action of HGF on TGF-beta remains unclear. We studied whether HGF has an inhibitory effect on TGF-beta production in vitro. METHODS: Mouse mesangial cells grown in 5 mM glucose containing DMEM (NG, normal glucose) were exposed with 25 mM glucose medium (HG, high glucose) alone or in the presence of recombinant HGF (10 ng/mL) for 48 hours. TGF-beta in culture supernatants were measured by sandwich enzyme-linked immunosorbent assay. Secretion of fibronectin and collagen Ia was measured by western blotting and immunoprecipitaiton. TGF-beta, fibronectin and collagen Ia mRNA levels were measured by real-time PCR and internally corrected with GAPDH. RESULTS: High glucose significantly increased TGF-beta secretion (p<0.05), but HGF could not prevent high glucose-induced TGF-beta release. High glucose increased the secretion of both fibronectin and collagen Ia, which was blocked by HGF (p<0.05). CONCLUSION: In cultured murine mesangial cells HGF did not have effect on TGF-beta production, but inhibited the secretion of both fibronectin and collagen Ia. These results suggest that HGF may have indirect inhibitory effect on the action of TGF-beta.

Keyword

Hepatocyte growth factor; Transforming growth factor; Fibronectin; Collagen Ia

MeSH Terms

Animals
Blotting, Western
Collagen*
Enzyme-Linked Immunosorbent Assay
Fibronectins*
Fibrosis
Glucose
Hepatocyte Growth Factor
Injections, Subcutaneous
Mesangial Cells*
Mice
Real-Time Polymerase Chain Reaction
Regeneration
RNA, Messenger
Transforming Growth Factor beta*
Transforming Growth Factors
Collagen
Fibronectins
Glucose
Hepatocyte Growth Factor
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factors