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Article Abstract
Objective: To explore the role of Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) in autosomal-dominant polycystic kidney disease (ADPKD).
Methods: NHERF1 and β-catenin protein were detected by immunohistochemistry and Western blotting of kidney tissue samples from patients with ADPKD and controls (normal kidney tissue [>5 cm from the foci] collected from patients undergoing unilateral nephrectomy for kidney cancer). NHERF1 and β-catenin protein and mRNA were quantified by Western blot and real-time fluorescent quantitative polymerase chain reaction, respectively, in kidney tissue samples from Han:SPRD (+/+) and (cy/+) rats. The effects of human recombinant NHERF1 on proliferation and cell cycle of ADPKD cyst-lining epithelial cells (WT9-12) were evaluated by MTT assay and flow cytometry, respectively.
Results: Levels of NHERF1 protein and mRNA were significantly lower, and β-catenin levels significantly higher, in patients with ADPKD and Han:SPRD (cy/+) rats, compared with control subjects and (+/+) rats, respectively. Exogenous recombinant NHERF1 significantly inhibited proliferation of WT9-12 cells and increased the proportion of cells in G(0)/G(1) phase.
Conclusions: ADPKD is associated with a decrease in NHERF1 protein and mRNA levels. Supplementing exogenous NHERF1 inhibited the proliferation of WT9-12 cells.
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