In vivo and in vitro evidence for increased expression of hgf
receptor in the kidney of diabetic rat.
Liu, Youhua, Evelyn M. Tolbert, Adam M. Sun, and Lance D. Dworkin.
Department of Medicine, Division of Renal Diseases, Rhode Island
Hospital, Brown University School of Medicine, Providence, Rhode
Island 02903
APStracts 3:0163F, 1996.
Renal hypertrophy develops early in the course of diabetes and has
been linked to progressive renal disease. Although the mechanism of
renal hypertrophy is unknown, evidence suggests that local
alterations in the production of one or more growth factors and/or
their receptors are crucial to this process. In this study, we
demonstrate that the c-met proto-oncogene product, a tyrosine kinase
receptor for hepatocyte growth factor (HGF), is increased in the
kidney of the diabetic rat. Northern blot analysis showed that renal
expression of the c-met gene was substantially increased in rats made
diabetic by administration of streptozotocin. Immunohistochemical
studies revealed that the protein for c-met was concordantly elevated
in cortical and medullar tubular epithelium following the onset of
diabetes. Moreover, in vitro studies demonstrated that short term
exposure to high glucose concentration markedly stimulated c-met
expression in cultured proximal tubular (OK) and inner medulla
collecting duct cells (mIMCD-3). The results of enhanced renal
expression of c-met together with elevated HGF indicate that the
HGF/c-met system is markedly activated in the diabetic rat. These
findings suggest that the HGF/c-met system may play a role in the
diabetic renal hypertrophy.
Received 29 November 1995; accepted in final form 29 August 1996.
APS Manuscript Number F402-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996