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This study aims to investigate the effects of TNF receptors associated factor 3 (TRAF3) on the signaling pathway and expression of downstream products of nuclear factor kappa B (NF-κB) in the epithelial cells of renal ducts in individuals with polycystic kidney disease (PKD). We observe the TRAF3 genic overexpression of the epithelial cells, which form a tubular branch structure, in polycystic kidneys and to explore the protective effect of TRAF3 on the cystogenesis and progression of PKD. Western blotting analysis was conducted to examine the signaling changes of NF-κB in PKD the epithelial cells and TRAF3 transgenic PKD epithelial cells. Changes in the downstream apoptosis factor and cell proliferation in PKD epithelial cells and TRAF3 transgenic PKD epithelial cells were detected. A three-dimensional matrigel culture experiment was performed to examine abnormal tubulomorphogenesis in vitro. The overexpression of TRAF3 significantly inhibited the signaling pathway of NF-κB in the PKD epithelial cells, downregulated the expression of downstream factors Bcl-2 and Bcl-xl, and significantly decreased cystic epithelial cell proliferation. Additional branch structures were observed in the PKD epithelial cells with a three-dimensional culture compared to wildtype cells. TRAF3 may likely induce apoptosis and resistance to proliferation and may be a new target to inhibit the cyst formation in PKD by regulating the NF-κB signaling pathway Bcl-2 and Bcl-xl activity. © 2017 IUBMB Life, 69(3):170-178, 2017 [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the molecular mechanism of miR‐182 in kidney fibrosis in polycystic kidney disease (PKD). We measured the expression of miR‐182 in kidney tissue of autosomal dominant PKD. Additionally, we investigated the relationship between miR‐182 and fibrotic protein by transfecting miR‐182 mimics and miR‐182 inhibitor into polycystic kidney cyst‐lined epithelial cells, respectively. Furthermore, we observed the interaction between transforming growth factor β1 (TGF‐β1) and miR‐182 and fibrinogen factors of cyst‐lined epithelial cells after TGF‐β1 intervention, and measured the expression of Smad2 and Smad3 protein. Results are presented as follows: (a) MiR‐182 was positively correlated with fibrosis of cyst‐lined epithelial cells; (b) TGF‐β1 could induce fibrosis of cyst‐lined epithelial cells; (c) the expression of miR‐182 had a remarkably impact on the fibrosis induced by TGF‐β1, but had little effect on the expression of TGF‐β1; (d) the expression of Smad3 protein in TGF‐β1 induce‐cyst‐lined epithelial cells was increased. TGF‐β1 and miR‐182 promoting the fibrosis of polycystic kidney cyst‐lined epithelial cells may be mediated by the TGF‐β1/Smad3 signaling pathway, of which Smad3 was an important regulator. [ABSTRACT FROM AUTHOR]