Zhang C, Zhou Y, Lai X, Zhou G, Wang H, Feng X, Chen Y, Wu Y, Wang T, Ma L
Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Department of Neurology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Transplant Proc. 2019 Apr;51(3):936-941. doi: 10.1016/j.transproceed.2019.01.080. Epub 2019 Jan 31.
Human umbilical cord-derived mesenchymal stem cells (HuMSCs) have been shown to suppress cardiac fibrosis; however, the underlying mechanisms are not fully understood. Recent studies have shown that endothelial-mesenchymal transition (EndMT) plays a crucial part in myocardial fibrosis. In the present study, we investigated the suppressive role of HuMSCs in cardiac fibrosis and related mechanisms in a rat dilated cardiomyopathy (DCM) model.
Male Lewis rats were randomly divided into 3 groups. Rats without any treatment served as a negative control group, while the DCM rats, which were generated by immunization with porcine myosin, were divided into 2 groups: a HuMSC group, in which HuMSCs (1 × 10 cells/rat) were injected intravenously, and a vehicle group, in which rats were injected with volume-matched solution containing no HuMSCs. Histologic and immunofluorescent measurements were used to evaluate the effects of HuMSCs on cardiac fibrosis and EndMT.
We observed a significant increase in myocardial fibrosis, and elevated EndMT in rats of the vehicle group were observed compared with those in the negative control group along with the increased activity of transforming growth factor (TGF)-β1/extracellular signal-regulated kinase (ERK) 1/2 signaling. Treatment with HuMSCs repressed the increase in myocardial fibrosis and EndMT observed in DCM rats, which correlated with decreased activity of TGF-β1/ERK1/2 signaling.
The HuMSCs attenuated cardiac fibrosis at least partly through the inhibition of TGF-β/ERK-induced EndMT.
人脐带间充质干细胞（HuMSCs）已被证明可抑制心脏纤维化；然而，其潜在机制尚未完全明确。最近的研究表明，内皮-间充质转化（EndMT）在心肌纤维化中起关键作用。在本研究中，我们在大鼠扩张型心肌病（DCM）模型中研究了HuMSCs对心脏纤维化的抑制作用及其相关机制。
雄性Lewis大鼠随机分为3组。未接受任何治疗的大鼠作为阴性对照组，而通过用猪肌球蛋白免疫产生的DCM大鼠分为2组：HuMSC组，静脉注射HuMSCs（1×10个细胞/大鼠）；以及载体组，注射不含HuMSCs的等体积溶液。采用组织学和免疫荧光测量来评估HuMSCs对心脏纤维化和EndMT的影响。
我们观察到载体组大鼠的心肌纤维化显著增加，与阴性对照组相比，EndMT升高，同时转化生长因子（TGF）-β1/细胞外信号调节激酶（ERK）1/2信号通路的活性增加。HuMSCs治疗抑制了DCM大鼠中观察到的心肌纤维化和EndMT的增加，这与TGF-β1/ERK1/2信号通路活性降低相关。
HuMSCs至少部分通过抑制TGF-β/ERK诱导的EndMT来减轻心脏纤维化。
