IGF-I binding and IGF-I mRNA expression in the post-ischemic regenerating rat kidney

The localization of IGF-I peptide and IGF-I mRNA was investigated in the post-ischemic regenerating rat kidney using immunohistochemistry and non-radioactive in situ hybridization techniques. In addition, the distribution and relative quantity of IGF-I binding sites were studied by autoradiographic ligand-binding techniques. Two and three days after the injury, morphological signs of an intense regenerative activity was evident. By this time a substantial number of the regenerating cells were stained with a monoclonal antibody against the M1 subunit of ribonucleotide reductase, a proliferative marker used. Low proliferative tubular cells, replacing those that had been injured, were seen lining the tubular basement membrane. By seven days, the morphology in the cortex was quite normalized, while cells of the S3 segments in the outer medulla remained dedifferentiated. The regenerative cells expressed IGF-I peptide and IGF-I mRNA in a transient manner and this was found to correlate better to cell differentiation than cell division. In addition, non-tubular cells, predominantly macrophages, expressed both the IGF-I peptide and the mRNA. The IGF-I binding was significantly increased in the regenerative zone at all times studied and began to decline at day seven. The binding characteristics were found to be compatible with binding to the IGF-I receptor. Altogether, these findings provide circumstantial evidence that IGF-I is of trophic importance in the regeneration of renal tubular cells. The data are compatible with a local production and action of IGF-I, suggesting an autocrine and/or paracrine mode of action during the regenerative process.