| Autor: |
Naijun Miao, Bao Wang, Dan Xu, Yanzhe Wang, Xinxin Gan, Li Zhou, Hong Xue, Wei Zhang, Xiaoxia Wang, Limin Lu |
| Předmět: |
|
| Zdroj: |
American Journal of Physiology: Renal Physiology; Feb2018, Vol. 314 Issue 2, pF269-F279, 11p |
| Abstrakt: |
Renal tubular injury is the hallmark of cisplatin-induced nephrotoxicity. Caspase-11, a member of the caspase family, plays an important role in inflammation and cell death. However, its role in cisplatin-induced renal tubular injury remains unclear. In cisplatin-treated mice, caspase-11 expression was significantly elevated and the expression of caspase-11 was mainly located in renal tubule. Inhibition of caspase-11 by small-interference RNA or its inhibitor wedelolactone attenuated cisplatin-induced renal dysfunction and tubular injury. In cultured primary renal tubular epithelial cells, cisplatin significantly promoted the expression and activation of caspase-11. Inhibition of caspase-11 by small-interference RNA reduced cisplatin-induced cell apoptosis. Overexpression of caspase-11 promoted cell apoptosis by activating the caspase-3- related cell apoptosis. Furthermore, coimmunoprecipitation results showed there was a direct interaction between caspase-11 and caspase-3, and the interaction was enhanced by cisplatin. The fluorescence confocal microscopy results showed that caspase-11 and caspase-3 were colocalized in the cytoplasm of renal tubular epithelial cells. These results demonstrate that caspase-11 plays an important role in cisplatin-induced renal tubular injury. Caspase-11 promotes renal epithelial cell apoptosis by activating the caspase-3-dependent apoptotic pathway. Caspase-11 might be a potential target for therapeutic treatment against cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
