Resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into esophageal fibroblasts via AKT signaling pathway

Xiujing Chen, Zihao Sun, Qian Wu, Lijuan Shao, Jiaxin Bei, Yiguang Lin, Hongjie Chen, Size Chen
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Abstract

Objectives: Resveratrol has been implicated in the differentiation and development of human umbilical cord mesenchymal stem cells. The differentiation of into esophageal fibroblasts is a promising strategy for esophageal tissue engineering. However, the pharmacological effect and underlying mechanism of resveratrol on human umbilical cord mesenchymal stem cells differentiation are unknown. Here, we investigated the effects and mechanism of resveratrol on the differentiation of human umbilical cord mesenchymal stem cells. Methods: Using a transwell-membrane coculture system to culture human umbilical cord mesenchymal stem cells and esophageal fibroblasts, we examined how resveratrol act on the differentiation of human umbilical cord mesenchymal stem cells. Immunocytochemistry, Sirius red staining, quantitative real-time PCR, and Western blotting were performed to examine collagen synthesis and possible signaling pathways in human umbilical cord mesenchymal stem cells. Results: We found that resveratrol promoted collagen synthesis and AKT phosphorylation. However, co-treatment of cells with resveratrol and the PI3K inhibitor LY294002 inhibited collagen synthesis and AKT phosphorylation. We demonstrated that resveratrol down-regulated the expression of IL-6, TGF-β, caspase-9, and Bax by activating the AKT pathway in human umbilical cord mesenchymal stem cell. Furthermore, resveratrol inhibited phosphorylated NF-ĸB in human umbilical cord mesenchymal stem cells. Conclusion: Our data suggest that resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into fibroblasts. The underlying mechanism is associated with the downregulation of IL-6 and TGF-β via the AKT pathway and by inhibiting the NF-ĸB pathway. Resveratrol may be useful for esophageal tissue engineering.
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白藜芦醇通过 AKT 信号通路促进人脐带间充质干细胞向食管成纤维细胞分化
目的白藜芦醇与人脐带间充质干细胞的分化和发育有关。将其分化为食管成纤维细胞是食管组织工程的一种有前途的策略。然而,白藜芦醇对人脐带间充质干细胞分化的药理作用和内在机制尚不清楚。在此,我们研究了白藜芦醇对人脐带间充质干细胞分化的影响和机制。研究方法采用跨孔-膜共培养系统培养人脐带间充质干细胞和食管成纤维细胞,研究白藜芦醇对人脐带间充质干细胞分化的作用。我们采用免疫细胞化学、天狼星红染色、定量实时 PCR 和 Western 印迹技术研究了人脐带间充质干细胞中胶原蛋白的合成和可能的信号通路。结果我们发现白藜芦醇能促进胶原蛋白合成和AKT磷酸化。然而,用白藜芦醇和 PI3K 抑制剂 LY294002 共同处理细胞会抑制胶原合成和 AKT 磷酸化。我们证实,白藜芦醇通过激活人脐带间充质干细胞的 AKT 通路,下调了 IL-6、TGF-β、caspase-9 和 Bax 的表达。此外,白藜芦醇还能抑制人脐带间充质干细胞中磷酸化的 NF-ĸB。结论我们的数据表明,白藜芦醇能促进人脐带间充质干细胞向成纤维细胞分化。其基本机制与通过 AKT 途径和抑制 NF-ĸB 途径下调 IL-6 和 TGF-β 有关。白藜芦醇可用于食管组织工程。
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来源期刊
CiteScore
4.00
自引率
0.00%
发文量
88
审稿时长
15 weeks
期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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