Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts.
Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts.
复制标题
DOI：
10.1139/cjpp-2013-0490
复制
发表时间：
2014-07
影响因子：
2.1
通讯作者：
Thodeti CK
中科院分区：
文献类型：
--
作者：
Shamhart PE;Luther DJ;Adapala RK;Bryant JE;Petersen KA;Meszaros JG;Thodeti CK
糖尿病是心血管疾病的独立风险因素，最终可能导致心肌病和心力衰竭。心脏成纤维细胞是生理性和病理性心脏重塑的重要介质，但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的研究，结果表明高血糖促进了心脏成纤维细胞的功能和分化。我们发现高糖处理增加了成年大鼠心脏成纤维细胞I型、III型和VI型胶原基因的表达。有趣的是，高血糖增加了CFs的迁移和增殖，而I型和III型胶原促进了这一过程。令人惊讶的是，我们发现短期高血糖短暂地抑制了ERK1/2的激活，但增加了AKT的磷酸化。最后，与低糖相比，高糖处理增加了心脏成纤维细胞向肌成纤维细胞的自发分化，增加了传代次数。综上所述，这些发现表明，高血糖通过调节心脏成纤维细胞的胶原表达、迁移、增殖和分化而诱导心脏纤维化。
Diabetes is an independent risk factor of 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 which 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 to low glucose. Taken together, these findings suggest that hyperglycemia induces cardiac fibrosis by modulating collagen expression, migration, proliferation and differentiation of cardiac fibroblasts.