Ablation of interleukin-17 alleviated cardiac interstitial fibrosis and improved cardiac function via inhibiting long non-coding RNA-AK081284 in diabetic mice.
Ablation of interleukin-17 alleviated cardiac interstitial fibrosis and improved cardiac function via inhibiting long non-coding RNA-AK081284 in diabetic mice.
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消融白介素 17 可通过抑制糖尿病小鼠的长链非编码 RNA-AK081284 减轻心脏间质纤维化并改善心脏功能。
DOI：
10.1016/j.yjmcc.2018.01.001
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发表时间：
2018-02
期刊：
影响因子：
--
通讯作者：
Pan ZW
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang YY;Li TT;Wang J;Jiang Y;Zhao Y;Jin XX;Xue GL;Yang Y;Zhang XF;Sun YY;Zhang ZR;Gao X;Du ZM;Lu YJ;Yang BF;Pan ZW
白细胞介素17（IL-17）在心脏间质纤维化的发病机制中起重要作用。本研究旨在探讨白细胞介素17（IL-17）在糖尿病性心肌病发生发展中的作用及其机制。敲除IL-17可改善链脲佐菌素（STZ）诱导的糖尿病小鼠的心功能，并显著减轻间质纤维化，表现为胶原mRNA表达减少和胶原沉积减少（Masson染色）。在培养的IL-17敲除的心脏成纤维细胞（CF）中，高糖处理诱导的胶原蛋白产生被消除。长链非编码RNA-AK 081284的水平在用高糖或IL-17处理的CF中增加。IL-17的敲除消除了高糖诱导的AK 081284的上调。过表达AK 081284可促进CFs胶原和TGFβ1的合成。应用针对AK 081284的siRNA可以减轻高糖和IL-17诱导的胶原和TGFβ1的产生。综上所述，IL-17的缺失能够减轻糖尿病小鼠心肌纤维化，改善心脏功能。IL-17/AK 081284/TGFβ1信号通路介导高糖诱导的胶原蛋白产生。本研究表明IL-17抑制剂对与纤维化相关的糖尿病性心肌病的治疗潜力。
Interleukin 17 (IL-17) plays an important role in the pathogenesis of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-17 in the development of diabetic cardiomyopathy and the underlying mechanisms.The level of IL-17 increased in both the serum and cardiac tissue of diabetic mice. Knockout of IL-17 improved cardiac function of diabetic mice induced by streptozotocin (STZ), and significantly alleviated interstitial fibrosis as manifested by reduced collagen mRNA expression and collagen deposition evaluated by Masson's staining. High glucose treatment induced collagen production were abolished in cultured IL-17 knockout cardiac fibroblasts (CFs). The levels of long noncoding RNA-AK081284 were increased in the CFs treated with high glucose or IL-17. Knockout of IL-17 abrogated high glucose induced upregulation of AK081284. Overexpression of AK081284 in cultured CFs promoted the production of collagen and TGFβ1. Both high glucose and IL-17 induced collagen and TGFβ1 production were mitigated by the application of the siRNA for AK081284.In summary, deletion of IL-17 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The IL-17/AK081284/TGFβ1 signaling pathway mediates high glucose induced collagen production. This study indicates the therapeutic potential of IL-17 inhibition on diabetic cardiomyopathy disease associated with fibrosis.
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影响因子：
3.7
作者：
Xie Y;Li M;Wang X;Zhang X;Peng T;Yang Y;Zou Y;Ge J;Chen H;Chen R
通讯作者：
Chen R
影响因子：
4.8
作者：
Valente AJ;Yoshida T;Gardner JD;Somanna N;Delafontaine P;Chandrasekar B
通讯作者：
Chandrasekar B
影响因子：
7.4
作者：
Liu H;Qin H;Chen GX;Liang MY;Rong J;Yao JP;Wu ZK
通讯作者：
Wu ZK
影响因子：
24
作者：
Galderisi, Maurizio
通讯作者：
Galderisi, Maurizio
影响因子：
20.1
作者：
Kumarswamy, Regalla;Bauters, Christophe;Thum, Thomas
通讯作者：
Thum, Thomas