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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts
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Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts

机译:高血糖可增强成年大鼠心脏成纤维细胞的功能和分化

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摘要

Diabetes is an independent risk factor for cardiovascular disease that can eventually cause cardiomyopathy and heart failure. Cardiac fibroblasts (CF) are the critical mediators of physiological and pathological cardiac remodeling; however, the effects of hyperglycemia on cardiac fibroblast function and differentiation is not well known. Here, we performed a comprehensive investigation on the effects of hyperglycemia on cardiac fibroblasts and show that hyperglycemia enhances cardiac fibroblast function and differentiation. We found that high glucose treatment increased collagen I, III, and VI gene expression in rat adult cardiac fibroblasts. Interestingly, hyperglycemia increased CF migration and proliferation that is augmented by collagen I and III. Surprisingly, we found that short term hyperglycemia transiently inhibited ERK1/2 activation but increased AKT phosphorylation. Finally, high glucose treatment increased spontaneous differentiation of cardiac fibroblasts to myofibroblasts with increasing passage compared with low glucose. Taken together, these findings suggest that hyperglycemia induces cardiac fibrosis by modulating collagen expression, migration, proliferation, and differentiation of cardiac fibroblasts.
机译:糖尿病是导致心血管疾病和心力衰竭的心血管疾病的独立危险因素。心脏成纤维细胞(CF)是生理和病理性心脏重构的关键介质。然而,高血糖对心脏成纤维细胞功能和分化的影响尚不清楚。在这里,我们对高血糖对心脏成纤维细胞的影响进行了全面调查,结果表明高血糖会增强心脏成纤维细胞的功能和分化。我们发现,高葡萄糖治疗可增加大鼠成年心脏成纤维细胞中胶原I,III和VI基因的表达。有趣的是,高血糖会增加CF的迁移和增殖,而胶原I和III会增加这种迁移。出人意料的是,我们发现短期高血糖症可暂时抑制ERK1 / 2激活,但增加AKT磷酸化。最后,与低葡萄糖相比,高葡萄糖治疗增加了心肌成纤维细胞自发分化为成肌纤维细胞的通道。综上所述,这些发现提示高血糖症通过调节心脏成纤维细胞的胶原蛋白表达,迁移,增殖和分化来诱导心脏纤维化。

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