Fibroblast growth factor receptors and their ligands in the adult rat kidney

Background. Fibroblast growth factors (FGFs) are a family of at least 21 heparin-binding proteins involved in many biological processes, both during development and in the adult, including cell proliferation, differentiation, and angiogenesis. FGFs mediate their effects through high-affinity tyrosine kinase receptors (FGFRs), which are encoded by four genes. The aims of the present study were to localize FGFR-1 through FGFR-3 in the normal adult rat kidney and to determine which functional FGFR variants and FGFs were expressed. Methods. Avidin-biotin-enhanced horseradish peroxidase immunohistochemistry was used on paraffin sections of rat kidney to localize FGFR-1 through FGFR-3, whereas reverse transcriptase-polymerase chain reaction was used to examine expression of the receptor variants and also of FGF-1 through FGF-10 in cortex, outer medulla, and inner medulla. Results. By immunohistochemistry, each receptor was localized to distinct and overlapping nephron segments, such that one or more FGFRs were localized to all nephron and collecting duct epithelia. FGFR-1 and FGFR-3 were localized to glomeruli, FGFR-3 to proximal tubules and FGFR-1 to thin limbs. FGFR-1 through FGFR-3 were localized to distal straight tu bules, with FGFR-1 and FGFR-3 localized to distal convoluted tubules. FGFR-1 and FGFR-3 were localized to medullary collecting ducts. in addition, FGFR-1 was localized to the smooth muscle of renal arteries. All seven FGFR variants were expressed in the cortex and outer medulla, with fewer FGFRs in the inner medulla. FGF-1, FGF-2, FGF-7, FGF-8, and FGF-9 were expressed in the kidney, with FGF-IO expression found only in the cortex. Conclusions. Mapping of these receptors is critical to the determination of the effects of FGF ligands in discrete regions of the kidney. The distributions of the FGFRs in the normal adult kidney and the restricted expression of FGF ligands suggest that specific FGFs have distinct and important roles in the maintenance of normal kidney structure and function.