Background
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.
Conclusion
The HuMSCs attenuated cardiac fibrosis at least partly through the inhibition of TGF-β/ERK-induced EndMT.
Methods
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 × 106 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.
Results
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.