Tanshinone IIA promotes cardiac differentiation and improves cell motility by modulating the Wnt/β‑catenin signaling pathway

丹参酮 IIA 通过调节 Wnt/β‑catenin 信号通路促进心脏分化并改善细胞运动

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作者:Kun Li #, Xiuyan Wang #, Chenxing Fan, Chunxia Wu, Shizheng Li, Hua Liu

Abstract

Although the cardiovascular pharmacological actions of Tanshinone IIA (TanIIA) have been extensively studied, research on its roles in cardiac regeneration is still insufficient. The present study employed the cardiac myoblast cell line H9c2 to evaluate the possible roles of TanIIA in cardiac regeneration. It was found that certain concentration of TanIIA inhibited cell proliferation by suppressing the expression of proteins related to the cell cycle [cyclin dependent kinase (CDK)4, CDK6 and cyclin D1] and proliferation [c‑Myc, octamer‑binding transcription factor 4 (Oct4) and proliferating cell nuclear antigen (PCNA)] without inducing apoptosis. In this process, the expression of cardiac troponin in the treated cells was significantly increased and the migration of the treated cells toward the wound area was significantly enhanced. Meanwhile, TanIIA inhibited the canonical signaling pathway through increasing the expression of glycogen synthase kinase 3β (GSK‑3β) and adenomatous polyposis coli (APC) and increased the expression of Wnt11 and Wnt5a in the noncanonical Wnt signaling pathway. Following β‑catenin agonist WAY‑262611 intervention, the effect of TanIIA on the promotion of cardiac differentiation and improved cell migration was significantly reduced. In conclusion, it was hypothesized that TanIIA could promote cardiac differentiation and improve cell motility by modulating the Wnt/β‑catenin signaling pathway. These results suggest that TanIIA may play beneficial roles in myocardial regeneration following stem cell transplantation.

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