Expression of NHERF-1, NHERF-2, PDGFR-α, and PDGFR-β in Normal Human Kidneys and in Renal Transplant Rejection

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Abstract
Sodium-hydrogen exchanger regulatory factor-1 and -2 (NHERF-1 and NHERF-2) are adaptor proteins that regulate renal electrolyte transport and interact with the platelet-derived growth factor receptors (PDGFR). The distribution of the NHERF proteins and PDGFR was studied in normal human kidneys and in renal transplant rejection using immunocytochemistry. In normal kidneys, NHERF-1 was detected in proximal tubules. NHERF-2 was detected in glomeruli, peritubular capillaries, and collecting duct principal cells. NHERF-2 was also weakly detected in the proximal tubule. PDGFR-β was detected in glomeruli but not in tubules while PDGFR-α was detected in renal tubules and minimally in glomeruli. Acute and chronic transplant rejection was associated with increased expression of PDGFR-α in tubules and expression in the glomeruli. PDGFR-β expression in the glomeruli was increased in transplant rejection and became detectable in tubules. Expression of NHERF-1 and NHERF-2 was not different in the patient groups. These results indicate that in contrast to the rat, both NHERF isoforms are detected in the human proximal tubule. In renal transplant rejection, there is increased expression of both PDGFR subtypes consistent with a role for PDGF in injury or repair.