Activity of keratinocyte growth factor-like substance extracted from rabbit liver on renal tubular cell growth during compensatory renal hyperplasia.

Abstract

In response to unilateral nephrectomy, the rabbit liver transiently produces 2 growth regulators for cultured renal cortical tubular cells: a tubular cell growth factor and a growth inhibitor. We report on the effects of the tubular cell growth factor on a variety of cell lines. The tubular cell growth factor activity was partially purified from the rabbit liver by using gel filtration and ion-exchange chromatography. The activity was monitored by the incorporation of iododeoxyuridine into DNA of cultured cells. Expression of the fibroblast growth factor receptor-2 in the rabbit kidney was determined by the immunoblot analysis. This growth factor stimulated the DNA synthesis in LLC-PK1 cells, LLC-RK1 cells, and human keratinocytes. It did not affect the growth of BS-C-1 cells, MDCK cells, BALB/c 3T3 fibroblasts, or rat parenchymal hepatocytes. The additive effect of this factor on the DNA synthesis of cultured tubular cells maximally was stimulated by insulin-like growth factor-I, basic fibroblast growth factor, and epidermal growth factor, but was not stimulated by keratinocyte growth factor. The amount of this activity also increased in the liver after sham operation. In the days after surgery, expression of fibroblast growth factor receptor-2, which includes the keratinocyte growth factor receptor, was down-regulated in the kidneys of both uninephrectomized and sham-operated rabbits. These findings indicate that tubular cell growth factor in the liver seems to be a keratinocyte growth factor, and acts in an endocrine manner in renal tubular hyperplasia.