Figure 1711

Expression of hepatocyte growth factor (HGF) mRNA and HGF receptor mRNA in kidney. While the liver is the major source of circulating HGF, the kidney also produces this growth-promoting peptide. Experiments utilizing in situ hybridization, immunohisto-chemistry, and reverse transcription-polymerase chain reaction (RT-PCR) have demonstrated HGF production by interstitial cells but not by any nephron segment. Presumably, these interstitial cells are macrophages and endothelial cells. Importantly, HGF expression in kidney actually increases within hours of an ischemic or toxic insult. This expression peaks within 6 to 12 hours and is followed a short time later by an increase in HGF bioactivity. HGF thus seems to act as a renotrophic factor, participating in regeneration via a paracrine mechanism; however, its expression is also rapidly induced in spleen and lung in animal models of acute renal injury. Reported levels of circulating HGF in patients with acute renal failure suggest that an endocrine mechanism may also be operational.

The receptor for HGF is the c-met proto-oncogene product. Receptor binding has been demonstrated in kidney in a variety of sites, including the proximal convoluted (PCT) and straight tubules, medullary and cortical thick ascending limbs (MTAL, CTAL), and in the outer and inner medullary collecting ducts (OMCD, IMCD). As with HGF peptide production, expression of c-met mRNA is induced by acute renal injury.

Membrane bound Pro-HGF

Matrix soluble pro-HGF

Membrane bound Pro-HGF

Matrix soluble pro-HGF

0 0

Post a comment