Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.
Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.
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鸢尾素抑制高葡萄糖诱导的内皮向间质转化，并对糖尿病心肌病发挥剂量依赖性双向作用。
DOI：
10.1111/jcmm.13360
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Zhang MX
中科院分区：
文献类型：
--
作者：
Liu X;Mujahid H;Rong B;Lu QH;Zhang W;Li P;Li N;Liang ES;Wang Q;Tang DQ;Li NL;Ji XP;Chen YG;Zhao YX;Zhang MX
新出现的证据表明，鸢尾素在糖尿病中提供有益的效果。然而，鸢尾素是否影响糖尿病心肌病（DCM）的发展仍不清楚。因此，我们研究了鸢尾素在糖尿病诱导的小鼠心肌功能障碍中的潜在作用和作用机制。通过注射链脲佐菌素在小鼠中诱导1型糖尿病，并向糖尿病小鼠施用重组鸢尾素（低或高剂量：0.5或1.5 μg/g体重/天，I. P.）或PBS培养16周。Irisin治疗没有改变糖尿病小鼠的血糖水平。然而，超声心动图和组织病理学测定的结果表明，低剂量的Irisin治疗减轻了糖尿病小鼠的心脏纤维化和左心室功能，而高剂量的Irisin未能减轻心室功能损害并增加胶原沉积。低剂量Irisin作用的潜在机制涉及Irisin介导的高糖诱导的内皮-间充质转化（EndMT）抑制;相反，高剂量Irisin治疗通过刺激MAPK（p38和ERK）信号传导和心脏成纤维细胞增殖和迁移增强高糖诱导的MMP表达。低剂量鸢尾素通过抑制高糖诱导的EndMT减轻DCM的发展。相比之下，高剂量的鸢尾素破坏了正常的MMP表达，并诱导心脏成纤维细胞增殖和迁移，导致过量的胶原沉积。因此，鸢尾素可以抑制高糖诱导的EndMT，并对DCM发挥剂量依赖性双向作用。
Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes‐induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r‐irisin (low or high dose: 0.5 or 1.5 μg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low‐dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high‐dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low‐dose irisin involved irisin‐mediated inhibition of high glucose‐induced endothelial‐to‐mesenchymal transition (EndMT); conversely, high‐dose irisin treatment enhanced high glucose‐induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low‐dose irisin alleviated DCM development by inhibiting high glucose‐induced EndMT. By contrast, high‐dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose‐induced EndMT and exert a dose‐dependent bidirectional effect on DCM.
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