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模拟微重力通过抑制 ERK/β-连环蛋白信号通路抑制鼠真皮成纤维细胞间充质干细胞的分化。

Simulated Microgravity Inhibits Rodent Dermal Fibroblastic Differentiation of Mesenchymal Stem Cells by Suppressing ERK/β-Catenin Signaling Pathway.

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.

出版信息

Int J Mol Sci. 2021 Oct 2;22(19):10702. doi: 10.3390/ijms221910702.

Abstract

Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to investigate the effect of simulated microgravity (SMG) on the differentiation of BMSCs into dermal fibroblasts and the related molecular mechanism. Here, using a 2D-clinostat device to simulate microgravity, we found that SMG inhibited the differentiation and suppressed the Wnt/β-catenin signaling and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2). After upregulating the Wnt/β-catenin signaling with lithium chloride (LiCl) treatment, we found that the effect of the differentiation was restored. Moreover, the Wnt/β-catenin signaling was upregulated when phosphorylation of ERK1/2 was activated with tert-Butylhydroquinone (tBHQ) treatment. Taken together, our findings suggest that SMG inhibits dermal fibroblastic differentiation of BMSCs by suppressing ERK/β-catenin signaling pathway, inferring that ERK/β-catenin signaling pathway may act as a potential intervention target for repairing skin injury under microgravity conditions.

摘要

研究表明,骨髓间充质干细胞(BMSCs)可分化为真皮成纤维细胞参与皮肤修复。然而,目前对于微重力如何影响空间中 BMSCs 的真皮成纤维细胞分化知之甚少。本研究旨在探讨模拟微重力(SMG)对 BMSCs 向真皮成纤维细胞分化的影响及其相关分子机制。在这里,我们使用二维回转器装置模拟微重力,发现 SMG 抑制了分化,并抑制了 Wnt/β-连环蛋白信号和细胞外调节蛋白激酶 1/2(ERK1/2)的磷酸化。在用氯化锂(LiCl)处理上调 Wnt/β-连环蛋白信号后,我们发现分化的作用得到了恢复。此外,用叔丁基对苯二酚(tBHQ)处理激活 ERK1/2 的磷酸化时,Wnt/β-连环蛋白信号被上调。综上所述,我们的研究结果表明,SMG 通过抑制 ERK/β-连环蛋白信号通路抑制 BMSCs 的真皮成纤维细胞分化,推断 ERK/β-连环蛋白信号通路可能作为微重力条件下修复皮肤损伤的潜在干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e66/8509498/f3c30f8dd644/ijms-22-10702-g001.jpg

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