PRIMARY STRUCTURE OF RAT HGF RECEPTOR AND INDUCED EXPRESSION IN GLOMERULAR MESANGIAL CELLS

The c-met protooncogene encodes a transmembrane tyrosine kinase recept or for hepatocyte growth factor (HGF). It has been widely suggested th at HGF and its receptor constitute a paracrine signaling system, in wh ich mesenchymally derived cells produce ligand that binds to the recep tor predominantly expressed on cells of epithelial origin. In this stu dy, we have isolated and completely sequenced the entire coding region of c-met cDNA from the rat kidney. The nucleotide sequence of the rat c-met cDNA revealed that the HGF receptor is encoded within single op en-reading frame as 190 kDa of a transmembrane glycoprotein consisting of 1,382 amino acids. Determination of c-met mRNA levels in various t issues revealed a widespread expression of c-met with the highest leve ls in kidney, lung, and liver. We found simultaneous induction of both HGF and its receptor gene expression by interleukin-g (IL-6) in prima ry cultured rat glomerular mesangial cells. The expression of HGF and c-met was remarkably stimulated following incubation of rat mesangial cells with IL-6, in a time- and dose-dependent manner. Our data sugges t that autocrine action of HGF may be achieved in vivo through simulta neous induction of both HGF and its receptor expression in renal mesen chymal cells.