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J. Biol. Chem., Vol. 266, Issue 34, 22781-22784, Dec, 1991
M Nagaike, S Hirao, H Tajima, S Noji, S Taniguchi, K Matsumoto and T Nakamura
Hepatocyte growth factor (HGF), a most potent growth factor for mature
hepatocytes may act as a trigger for liver regeneration. We reported that
HGF strongly stimulates DNA synthesis of rabbit renal tubular cells in
secondary culture (Igawa, T., Kanda, S., Kanetake, H., Saitoh, Y.,
Ichihara, A., Tomita, Y., and Nakamura, T. (1991) Biochem. Biophys. Res.
Commun. 174, 831-838). To investigate whether or not HGF is involved in
renal regeneration, we examined changes in HGF mRNA, HGF activity, and HGF
receptor in the rat kidney following unilateral nephrectomy or treatment
with carbon tetrachloride (CCl4). In the intact kidney, the HGF mRNA
increased markedly reaching a maximum 6 h after unilateral nephrectomy,
followed by an increase of HGF activity at 12 h after the surgery. The
marked increase in HGF mRNA and HGF activity was also found in the kidney
of rats treated with CCl4. Results of in situ hybridization suggested that
cells producing HGF in the kidney are endothelial cells. The number of HGF
receptors on renal plasma membranes decreased to 30% of the normal value 12
h after unilateral nephrectomy, with no change in the Kd value. The HGF
receptor was greatly diminished 24 h after the operation, and recovery to
60% of the normal level was evident 1 week after the operation. Because the
decrease in HGF binding may result from internalization of the HGF
receptor, the HGF may bind to its receptor in vivo and act as a mitogen for
renal epithelial cells. HGF may function as a renotropic factor during
renal regeneration after kidney injury.
Renotropic functions of hepatocyte growth factor in renal regeneration after unilateral nephrectomy
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
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