心脏纤维化
糖尿病性心肌病
纤维化
2型糖尿病
医学
糖尿病
内科学
内分泌学
下调和上调
心力衰竭
体内
链脲佐菌素
心肌病
生物
生物化学
生物技术
基因
作者
Yuanyuan Tian,Zhenyu Wang,Xiangyu Zheng,Wenjing Song,Lu Cai,Madhavi J. Rane,Yuguang Zhao
标识
DOI:10.1016/j.taap.2021.115654
摘要
Diabetic cardiomyopathy (DCM) is a serious diabetic complication that lacks effective preventive or therapeutic approaches. Wild-type and Klf15 knockout (Klf15-KO) mice were fed with either high fat diet (HFD, 60% kcal from fat) or normal diet (ND, 10% kcal from fat) for 3 months and then injected with streptozotocin or vehicle, to induce type 2 diabetes (T2D). All T2D and age-matched control mice were treated with or without SDF-1β at 5 mg/kg body-weight twice a week and also continually received HFD or ND for 3 months. At the end of 6-month study, after cardiac functions were measured, mice were euthanized to collect heart tissue. For in vitro mechanistic study, H9c2 cells were exposed to palmitate to mimic in vivo condition of T2D. SDF-1β prevented T2D-induced cardiac dysfunction and fibrosis and T2D-down-regulated KLF15 expression in wild-type diabetic heart tissue. However, the preventive effects of SDF-1β on both KLF15 expression and fibrosis was abolished, with partial cardiac protection in Klf15-KO/T2D mice. These results demonstrate partial KLF15-dependence for SDF-1β's cardiac fibrotic protection from T2D, but not on SDF-1β's protective effects on T2D-induced cardiac dysfunction. Further study showed that SDF-1β inhibited palmitate-induced cardiomyocyte fibrosis through its receptor CXCR7-mediated activation of p38β MAPK signaling pathway.
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