Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model.
Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model.
复制标题
诱导细胞死亡的 DFF45 样效应 C 基因沉默可减轻 2 型糖尿病大鼠模型中的肺血管重塑
DOI：
10.1111/jdi.12768
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发表时间：
2018-07
影响因子：
3.2
通讯作者：
Ti Y
中科院分区：
文献类型：
--
作者：
Sui DX;Zhou HM;Wang F;Zhong M;Zhang W;Ti Y
细胞死亡诱导的DFF45样效应子C(CIDEC)与胰岛素抵抗和代谢综合征的发生密切相关。我们的目的是研究CIDEC基因沉默是否可以减轻2型糖尿病大鼠模型的肺血管重构。我们建立了一种2型糖尿病大鼠模型。然后将携带CIDEC小干扰核糖核酸的腺病毒注射到颈静脉以沉默CIDEC基因。苏木精-伊红、天狼星红染色后检测肺小动脉重构指标。用增殖细胞核抗原免疫组织化学染色检测大鼠肺血管平滑肌细胞的增殖情况。用末端脱氧核苷酸转移酶dUTP缺口末端标记法和免疫印迹法检测细胞凋亡。免疫印迹法检测细胞内信号通路蛋白表达水平。组织学分析显示，2型糖尿病大鼠肺血管外膜和中层厚度明显增加。免疫组织化学显示，2型糖尿病大鼠肺血管内皮细胞增殖细胞核抗原阳性细胞增多，CIDEC基因沉默后，增殖细胞核抗原阳性细胞相应减少。Western blotting检测切割的caspase-3和切割的聚(二磷酸腺苷-核糖)聚合酶显示糖尿病大鼠细胞凋亡增加，CIDEC过表达。末端脱氧核苷酸转移酶dUTP缺口末端标记反应显示，细胞凋亡主要发生在内皮细胞。Western blotting分析显示糖尿病大鼠CIDEC过度表达，磷酸化的单磷酸腺苷活化蛋白激酶-α的表达显著降低。CIDEC基因沉默后，磷酸化的单磷酸腺苷活化蛋白激酶-α表达上调。CIDEC/5‘-单磷酸活化蛋白激酶信号通路可能成为治疗2型糖尿病肺血管病变的潜在靶点。
Cell death‐inducing DFF45‐like effector C (CIDEC) was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetes rat model. We built a type 2 diabetes rat model. An adenovirus harboring CIDEC small interfering ribonucleic acid was then injected into the jugular vein to silence the CIDEC gene. After hematoxylin–eosin and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of proliferating cell nuclear antigen was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling reaction and western blotting. The levels of signaling pathway proteins expression were measured by western blotting analyses. Histological analysis of the pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetes rats. Immunohistochemistry showed that more proliferating cell nuclear antigen‐positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetes rats; and after CIDEC gene silencing, proliferating cell nuclear antigen positive cells decreased accordingly. Cleaved caspase‐3 and cleaved poly (adenosine diphosphate‐ribose) polymerase measured by western blotting showed increased apoptosis with overexpressed CIDEC in diabetes. Terminal deoxynucleotidyl transferase dUTP nick end labeling reaction showed that the apoptosis mainly occurred in endothelial cells. Western blotting analysis showed CIDEC overexpression in rats with diabetes, and phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α was upregulated. The CIDEC/5′ monophosphate‐activated protein kinase signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes patients.
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影响因子：
2.1
作者：
Koskenvuo, Juha W.;Mirsky, Rachel;Zhang, Yan;Angeli, Franca S.;Jahn, Sarah;Alastalo, Tero-Pekka;Schiller, Nelson B.;Boyle, Andrew J.;Chatterjee, Kanu;De Marco, Teresa;Yeghiazarians, Yerem
通讯作者：
Yeghiazarians, Yerem
影响因子：
2.7
作者：
Moral-Sanz, Javier;Lopez-Lopez, Jose G.;Moreno, Laura
通讯作者：
Moreno, Laura
影响因子：
20.1
作者：
Lai YC;Potoka KC;Champion HC;Mora AL;Gladwin MT
通讯作者：
Gladwin MT
影响因子：
20.1
作者：
Paulin, Roxane;Michelakis, Evangelos D.
通讯作者：
Michelakis, Evangelos D.
影响因子：
5.8
作者：
Sakao S;Tatsumi K;Voelkel NF
通讯作者：
Voelkel NF