Transient Reciprocal Change of Renal Hepatocyte Growth Factor and Transforming Growth Factor-Beta1 May Relate to Renal Hypertrophy in Rats with Liver Injury or Unilateral Nephrectomy

Abstract

We examined an animal model of liver injury using ligation of the common bile duct (CBD) in young rats to observe nephromegaly and to determine plasma and renal changes in hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta1. To examine the role of TGF-beta1 in the process of compensatory renal growth, renal tissue HGF, TGF- beta1, TGF-beta1 mRNA, and c-met protein were measured. Plasma HGF level decreased significantly at 1 wk, and plasma TGF-beta1 level also decreased at 1 wk and remained low at 2 wk after surgery in CBD ligation rats. Increased renal HGF /TGF-beta1 ratio was noted at 2 wk, followed by a higher kidney weight/body weight ratio and an elevated protein/DNA ratio at 3 wk after operation in CBD ligation rats. The increased renal HGF/TGF- beta1 ratio in CBD ligation rats was mainly attributed to elevated renal HGF levels. Renal HGF/ TGF-beta1 ratio was also elevated at 12 h after unilateral nephrectomy. This elevated renal HGF/TGF-beta1 resulted exclusively from low renal TGF-beta1. Renal TGF-beta1 mRNA decreased significantly at 12-24 h after surgery in unilateral nephrectomized rats, whereas renal c-met receptor protein levels increased. Transient reciprocal change of HGF and TGF-beta1 manifesting as an increased renal HGF/TGF- beta1 ratio soon after uninephrectomy and later during CBD ligation suggests the probable role of TGF-beta1 in renal growth control and its possible initiating of renal hypertrophy in liver injury or unilateral nephrectomy. kidney weight/body weight ratio and an elevated protein/DNA