Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction.
Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction.
复制标题
Gasdermin E 缺失可减轻输尿管梗阻和 5/6 肾切除术引起的肾纤维化和肾功能不全
DOI：
10.3389/fcell.2021.754134
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Jia Z
中科院分区：
文献类型：
--
作者：
Wu M;Xia W;Jin Q;Zhou A;Wang Q;Li S;Huang S;Zhang A;Zhang Y;Li Y;Jia Z
肾纤维化有助于各种慢性肾脏疾病（CKDs）的肾功能障碍。肾纤维化可由肾小管细胞死亡和炎症引起。据报道，在几种肾损伤模型中，气皮蛋白E （GSDME）的缺失可以抑制肾小管细胞的焦亡。然而，需要更多的证据来证实GSDME在不同CKDs中调节肾纤维化和肾功能的作用。在我们的研究中，N-GSDME在体内和体外CKD模型中的表达均显著升高。GSDME缺失在单侧输尿管结肠炎（UUO）和5/6肾切除术（5/6Nx）模型中均可减轻肾脏纤维化和炎症，同时肾功能减弱。N-GSDME过表达对UUO肾脏和TGF-β1处理的肾小管上皮细胞的纤维化反应有不利影响。此外，给予caspase-3抑制剂Z-DEVD-FMK，抑制caspase-3介导的GSDME切割，在体内和体外均可防止肾纤维化。总的来说，这些结果提供了证据，证明GSDME的激活可能通过促进CKD的炎症反应，在调节肾纤维化和肾功能障碍方面至关重要。这些发现可能为识别新的CKDs治疗靶点提供新的见解。
Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs.
登录
查看更多内容
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng
影响因子：
64.8
作者：
Wang, Yupeng;Gao, Wenqing;Shao, Feng
通讯作者：
Shao, Feng
Caspase-11对gasdermin D的裂解促进急性肾损伤中肾小管上皮细胞焦亡和尿IL-18排泄
影响因子：
19.6
作者：
Miao, Naijun;Yin, Fan;Lu, Limin
通讯作者：
Lu, Limin
影响因子：
4.6
作者：
Guo H;Bi X;Zhou P;Zhu S;Ding W
通讯作者：
Ding W
影响因子：
2.9
作者：
Schnaper HW
通讯作者：
Schnaper HW