Expression of Na⁺/H⁺ exchanger regulatory factor 1 in autosomal-dominant polycystic kidney disease

Abstract

Objective: To explore the role of Na þ /H þ exchanger regulatory factor 1 (NHERF1) in autosomal-dominant polycystic kidney disease (ADPKD). Methods: NHERF1 and b-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 b-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 (þ/þ) and (cy/þ) 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 b-catenin levels significantly higher, in patients with ADPKD and Han:SPRD (cy/þ) rats, compared with control subjects and (þ/þ) 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.

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

“…When NHERF1 is localized at the plasma membrane, the protein preserves the epithelial polarity through the formation of tight junctions (14), targets several proteins to the apical or basolateral membrane (15,16) and cooperates in the formation and assembly of protein complexes at the microvillus (17). Instead, when located within the cell NHERF1 reduces the integrity of the actin cytoskeleton, by increasing a-actinin IV ubiquitination and degradation (18).…”

New roles of the Na+/H+ exchange regulatory factor 1 scaffolding protein: a review

“…NHERF1 colocalization with proteins has been implicated in cell polarity through the formation of tight junctions (7), targeting of proteins to the apical or basolateral membrane (3,22,54), microvillus formation (18), and assembly of protein complexes. For example, in proximal tubules, NHERF1 acts as a scaffold for the PTH receptor, the downstream signaling molecule adenylyl cyclase, and the target protein Npt2a and anchors this complex in the apical membrane through ezrin binding.…”