Hepatocyte growth factor: A regulator of extracellular matrix genes in mouse mesangial cells

The potential rule of hepatocyte growth factor (HGF) in regulating extracellular matrix in mouse mesangial cells (MMC) was evaluated. Functional HGF receptors were detected in MMC by HGF-induced extracellular acidification, a response that was inhibited by the HGF inhibitor HGF/NK2, a splice variant expressing the N-terminal domain through the second kringle domain. HGF also increased fibronectin and collagen alpha 1 (IV) mRNA levels in these cells; the increases were associated with a concentration dependent increase in transcriptional activity of the collagen oil (IV) gene. HGF also stimulated fibronectin and collagen alpha 1 (IV) mRNA levels in primary rabbit proximal tubule epithelial cells. To evaluate the potential consequences of chronic elevation of HGF on renal function, HGF was administered continuously for 18 days to normal and diabetic C57BLKS/J lepr(db) mice. In the diabetic mice, HGF reduced creatinine clearance and increased microalbuminuria, indicating that chronic exposure to HGF impairs renal function. Thus, chronically elevated HGF:may contribute to the progression of chronic renal disease in diabetes by decreasing the glomerular filtration rate and possibly promoting the accumulation of extracellular matrix. BIOCHEM PHARMACOL 59;7:847-853, 2000. (C) 2000 Elsevier Science Inc.