Kidney Institute and Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Sci Rep. 2017 Mar 20;7:44892. doi: 10.1038/srep44892.
Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO. The results indicate that the intrinsic pathway of apoptosis contributes significantly to the tubular apoptosis and renal interstitial fibrosis in kidney diseases.
间质纤维化是慢性肾脏病的一种常见病理特征，常伴有肾组织细胞凋亡。为了确定相关的凋亡途径及其在肾间质纤维化中的作用，我们建立了一种小鼠模型，该模型特异性地从肾脏近端小管中敲除了凋亡内在途径中的两个关键基因 Bax 和 Bak，并用该模型研究了单侧输尿管梗阻 (UUO) 后肾脏细胞凋亡和间质纤维化。结果表明，从近端小管敲除 Bax 和 Bak 的双基因敲除可减轻 UUO 时肾小管细胞凋亡，并抑制肾间质纤维化。这些结果表明，凋亡的内在途径对肾脏疾病中的肾小管凋亡和肾间质纤维化有重要贡献。
