Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus
Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus
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DOI：
10.1111/jcmm.15143
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发表时间：
2020-03
影响因子：
5.3
通讯作者：
Yanrong Zhu;Xiao-Xin Jiang;Peng Ye;Zhimei Wang;Ya-guo Zheng;Zhizhong Liu;Shaoliang Chen;
中科院分区：
文献类型：
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作者：
Yanrong Zhu;Xiao-Xin Jiang;Peng Ye;Zhimei Wang;Ya-guo Zheng;Zhizhong Liu;Shaoliang Chen;
糖尿病引起的血管功能障碍是动脉硬化的重要因素。先前的研究表明，在高血压和糖尿病期间，AKAP 150通过加强BK通道的重塑来促进血管张力增强。然而，AKAP 150和BK通道之间的相互作用仍有待讨论。在这项研究中，我们研究了糖尿病中受损的BK通道介导的血管功能障碍的调节。使用AKAP 150缺失小鼠（AKAP 150-/-）和野生型（WT）对照小鼠（C57 BL/6 J），通过腹腔注射链脲佐菌素诱导糖尿病。我们发现AKAP 150的敲除逆转了糖尿病小鼠和AKAP 150 −/−糖尿病小鼠的血管重塑和纤维化。Akt/GSK 3 β信号传导受损导致糖尿病小鼠胰岛中BK-β1表达降低，而AKAP 150沉默增加了HG培养基处理的MOVAS细胞中Akt磷酸化和BK-β1表达。Akt活性的抑制导致BK-β1表达的降低，并且用AKAP 150 siRNA处理抑制了HG处理的MOVAS细胞核中的GSK 3 β表达。AKAP 150的敲除通过Akt/GSK 3 β信号通路逆转糖尿病中受损的BK通道介导的血管功能障碍。
Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel‐mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150−/−) and wild‐type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150−/− diabetic mice. Impaired Akt/GSK3β signalling contributed to decreased BK‐β1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK‐β1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK‐β1 expression, and treatment with AKAP150 siRNA suppressed GSK3β expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus.