IN-VITRO DEMONSTRATION OF A MITOGENIC ACTIVITY IN RENAL TISSUE-EXTRACTS DURING REGENERATIVE HYPERPLASIA

Normal Pat kidney (NRK-52E) cells, an established cell line of renal o rigin, were used as a bioassay system to reveal a possible mitogenic a ctivity in tissue extracts prepared from kidneys undergoing tubular re generation. Acute tubular injury was induced in female Wistar rats by a 4-day treatment with gentamicin at daily doses of 50 or 100 mg/kg tw ice daily. Animals were killed either 1 or 4 days after cessation of g entamicin administration. Proximal tubule regeneration in treated anim als was confirmed by morphological examination after proliferating cel l nuclear antigen staining. Tissue extracts from regenerating kidneys stimulated DNA synthesis in growth-arrested cells to a higher extent t han extracts hom intact kidneys. Sera from treated and control animals showed no difference with respect to mitogenic activity. The mitogeni c effect of tissue. extracts was sensitive to the tyrosine kinase inhi bitor tyrphostin A46. The call proliferative response to regenerating kidney extracts, but not that to intact kidney extracts, was pertly su ppressed by the addition of anti-insulin-like growth factor I (anti-IG F-I) antiserum, These data indicate that nephrogenic repair entails an elevation of biologically active IGF-I in kidney tissue.