| Autor: |
Xiao-Long, Li, Jing, Liu, Xiao-Shan, Chen, Li-Min, Cheng, Wei-Ling, Liu, Xing-Feng, Chen, Yue-Jiao, Li, Yong-Yuan, Guan, Xin, Zeng, Yan-Hua, Du |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
British journal of pharmacologyREFERENCES. 179(12) |
| ISSN: |
1476-5381 |
| Popis: |
Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a CaMasson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular ClTMEM16A expression was significantly up-regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high-fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A-shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh-A01 or T16Ainh-A01 effectively prevented UUO-induced renal fibrosis and decreased protein expression of fibronectin, α-SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF-β1-induced epithelial-mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF-β1 increased [ClBlockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing [Cl |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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