IN-VIVO AND IN-VITRO EVIDENCE FOR INCREASED EXPRESSION OF HGF RECEPTOR IN KIDNEY OF DIABETIC RAT

Renal hypertrophy develops early in the course of diabetes and has bee n linked to progressive renal disease. Although the mechanism of renal hypertrophy is unknown, evidence suggests that local alterations in t he production of one or more growth factors and/or their receptors are crucial to this process. In this study, we demonstrate that the c-net protooncogene product, a tyrosine kinase receptor for hepatocyte grow th factor (HGF), is increased in the kidney of the diabetic rat. North ern blot analysis showed that renal expression of the c-met gene was s ubstantially increased in rats made diabetic by administration of stre ptozotocin. Immunohistochemical studies revealed that the protein for c-met was concordantly elevated in cortical and medullar tubular epith elium following the onset of diabetes. Moreover, in vitro studies demo nstrated that short-term exposure to high glucose concentration marked ly stimulated c-met expression in cultured proximal tubular (opossum k idney) and inner medulla collecting duct cells (mIMCD-3). The results of enhanced renal expression of c-met together with elevated HGF indic ate that the HGF/c-met system is markedly activated in the diabetic ra t. These findings suggest that the HGF/c-met system may play a role in the diabetic renal hypertrophy.