Sun Liping, Hu Chaofeng, Zhang Xinzhou
Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.
Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China.
IUBMB Life. 2017 Mar;69(3):170-178. doi: 10.1002/iub.1601. Epub 2017 Feb 10.
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.
本研究旨在探讨肿瘤坏死因子受体相关因子3（TRAF3）对多囊肾病（PKD）患者肾导管上皮细胞核因子κB（NF-κB）信号通路及下游产物表达的影响。我们观察多囊肾中形成管状分支结构的上皮细胞中TRAF3基因的过表达情况，并探讨TRAF3对PKD囊肿形成和进展的保护作用。采用蛋白质印迹分析检测PKD上皮细胞和TRAF3转基因PKD上皮细胞中NF-κB的信号变化。检测PKD上皮细胞和TRAF3转基因PKD上皮细胞中下游凋亡因子和细胞增殖的变化。进行三维基质胶培养实验以检测体外异常的肾小管形态发生。TRAF3的过表达显著抑制了PKD上皮细胞中NF-κB的信号通路，下调了下游因子Bcl-2和Bcl-xl的表达，并显著降低了囊性上皮细胞的增殖。与野生型细胞相比，三维培养的PKD上皮细胞中观察到额外的分支结构。TRAF3可能诱导细胞凋亡并抵抗增殖，可能是通过调节NF-κB信号通路中Bcl-2和Bcl-xl的活性来抑制PKD囊肿形成的新靶点。©2017国际生物化学与分子生物学联盟生命科学出版社，69(3):170 - 178, 2017。
