Resveratrol controlled the fate of porcine pancreatic stem cells through the Wnt/β-catenin signaling pathway mediated by Sirt1

Porcine pancreatic stem cells (PSCs) are considered promising transplant materials that may be used to treat diabetes, but some problems, such as insufficient cell number and low differentiation efficiency, should be solved before its clinical application. Resveratrol is a natural polyphenolic compound that can alleviate the complications of diabetes. In this study, we aimed to explore the specific effect of resveratrol on porcine PSCs. We treated porcine PSCs with 10 μM, 25 μM resveratrol to explore the effect of resveratrol on porcine PSCs. We found that 10 μM resveratrol improved the proliferation of porcine PSCs, increased the expression of A-β-catenin (active β-catenin), Pcna, C-Myc, Bcl-2 and sirtuin-1 (Sirt1), and decreased the expression of P53, Caspase3. While 25 μM resveratrol had almost opposite effect compared with 10 μM resveratrol group. The utilization of Dickkopf-related protein 1 (DKK1, Wnt signaling pathway inhibitor) and nicotinamide (Sirt1 inhibitor) suggested that resveratrol regulated cell proliferation by controlling Wnt signaling pathway and this effect was mediated by Sirt1. Our results further revealed that 10 μM resveratrol promoted the formation of β-like cells regulated by Wnt/β-catenin signal pathway. Relatively low-dose resveratrol could improve porcine PSCs fate. It lays theoretical foundation for diabetes treatment with cell transplantation in future.

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