TISSUE DISTRIBUTION OF HEPATOCYTE GROWTH-FACTOR RECEPTOR AND ITS EXCLUSIVE DOWN-REGULATION IN A REGENERATING ORGAN AFTER INJURY

Using I-125-labeled hepatocyte growth factor (HGF) as a ligand, we examined the tissue distribution of the HGF receptor in adult rats. Specific binding of I-125-HGF was detected in the plasma membranes of liver, spleen, kidney, lung, adrenal gland, pituitary, and thyroid. Scatchard analysis of HGF binding in liver, spleen, kidney, lung, and 'adrenal gland revealed the presence of a single class of high affinity receptor with a dissociation constant (K(d)) of 20-30 pM. The maximum number of binding sites (B(max)) was determined to be 400-3,000 sites per ng of plasma membrane protein, the highest number being in the liver. Such a wide distribution of a high affinity HGF receptor indicates that HGF may be a multifunctional growth factor, targeting to a variety of organs, and not restricted to liver. After 70% partial hepatectomy, specific binding of I-125-HGF to membranes of the residual liver rapidly decreased, but there was no change in the kidney, lung, and spleen. On the other hand, after unilateral nephrectomy rapid down-regulation of the HGF receptor was clearly evident in the remaining kidney, but not in other organs including the liver. These findings suggest the presence of control mechanisms governing HGF receptor function only in a regenerating organ after injury.