Xu Shuanshuan, Sun Fen, Ren Lipeng, Yang Hong, Tian Na, Peng Sha
College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, P. R., China.
PLoS One. 2017 Oct 26;12(10):e0187159. doi: 10.1371/journal.pone.0187159. eCollection 2017.
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.
猪胰腺干细胞（PSCs）被认为是有望用于治疗糖尿病的移植材料，但在其临床应用之前，一些问题，如细胞数量不足和分化效率低等，需要解决。白藜芦醇是一种天然多酚化合物，可缓解糖尿病并发症。在本研究中，我们旨在探讨白藜芦醇对猪PSCs的具体作用。我们用10μM、25μM白藜芦醇处理猪PSCs，以探究白藜芦醇对猪PSCs的影响。我们发现，10μM白藜芦醇可改善猪PSCs的增殖，增加A-β-连环蛋白（活性β-连环蛋白）、增殖细胞核抗原（Pcna）、原癌基因C-Myc、凋亡抑制基因Bcl-2和沉默信息调节因子1（Sirt1）的表达，并降低P53、半胱天冬酶3（Caspase3）的表达。而25μM白藜芦醇与10μM白藜芦醇组相比，作用几乎相反。使用Dickkopf相关蛋白1（DKK1，Wnt信号通路抑制剂）和烟酰胺（Sirt1抑制剂）表明，白藜芦醇通过控制Wnt信号通路调节细胞增殖，且这种作用由Sirt1介导。我们的结果进一步表明，10μM白藜芦醇促进了由Wnt/β-连环蛋白信号通路调控的β样细胞的形成。相对低剂量的白藜芦醇可改善猪PSCs的命运。这为未来通过细胞移植治疗糖尿病奠定了理论基础。
