AMYLIN AS A GROWTH-FACTOR DURING FETAL AND POSTNATAL-DEVELOPMENT OF THE RAT-KIDNEY

We have previously reported that amylin has mitogenic actions on tubul ar epithelial cells isolated from mature rat kidney and cultured in vi tro. In experiments using in situ hybridization, we have demonstrated that amylin mRNA can be detected transiently in rat metanephros from e mbryo day 17 (E17) to postnatal day 3 (PN3). These transcripts are loc alized in the sub-nephrogenic zone. RT-PCR was performed using oligonu cleotide primers for rat amylin and mRNA extracted from fetal body (E1 9), PN1 and PN5 metanephroi, and adult rat kidney. These results corro borate the finding, using in situ hybridization, that there is a windo w of expression of rat amylin in the developing kidney in the perinata l period. During this period tubular elongation is evident and amylin peptide, detected by immunohistochemical staining, is found associated with developing tubules. Some of these tubules also express a brush b order glycoprotein, detected by immunohistochemical staining. Amylin a cts as a mitogen with primary cultures of proximal tubular epithelial cells from PN4 renal cortex. An amylin antagonist inhibited this mitog enic action suggesting that this was mediated by amylin receptors as p reviously described. We suggest that amylin peptide is biosynthesized in the developing proximal tubules, acts in an autocrine fashion to pr omote the proliferation and differentiation of brush border epithelial cells and hence plays an important role as a growth factor in the dev elopment of the kidney.