HEPATOCYTE GROWTH-FACTOR PREVENTS RENAL FIBROSIS AND DYSFUNCTION IN AMOUSE MODEL OF CHRONIC RENAL-DISEASE

Chronic renal disease (CRD) is generally thought to be incurable, exce pt through renal transplantation, and the number of patients with CRD is on the increase. Glomerulosclerosis and tubulointerstitial fibrosis represent the morphological equivalent of end-stage CRD. In this stud y, we demonstrated the preventive effect of hepatocyte growth factor ( HGF) on the progression of renal dysfunction and fibrosis, using a spo ntaneous mouse model for CRD (ICGN strain). The mice progressively dev eloped glomerular sclerotic injury, tubular atrophy, and renal dysfunc tion until they were 17 wk of age. When recombinant HGF was injected i nto these mice during a 4-wk-period (from weeks 14-17 after birth), DN A synthesis of tubular epithelial cells was found to be 4.4-fold highe r than in mice without HGF injection, thereby suggesting tubular paren chymal expansion promoted by HGF. Notably, HGF suppressed the expressi on of transforming growth factor-beta and of platelet-derived growth f actor as well as myofibroblast formation in the affected kidney. Conse quently, the onset of tubulointerstitial fibrosis was almost completel y inhibited by HGF, while HGF attenuated the progression of glomerulos clerosis, both leading to preventing manifestation of renal dysfunctio n, From our results, supplement therapy with HGF may be taken into con sideration as a novel option for prevention and treatment of CRD.