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.
Highlights
Studies have found that astronauts often have skin problems such as allergic rashes and effusion, a significant reduction in elasticity, obvious thinning of the dermis, increased skin sensitivity, and delayed wound healing [1,2,3]
We evaluated the mRNA expression of collagen I (Col I), collagen III (Col III), Desmin, and fibroblast-specific protein-1 (FSP1) [17,18], highly specific markers in dermal fibroblasts after treatment of Bone marrow-derived mesenchymal stem cells (BMSCs) with connective tissue growth factor (CTGF)
We found that the mRNA expression level of Col I, Col III, Desmin, and FSP-1 in induced BMSCs for 7 days and 14 days were significantly increased compared to that of
Summary
Studies have found that astronauts often have skin problems such as allergic rashes and effusion, a significant reduction in elasticity, obvious thinning of the dermis, increased skin sensitivity, and delayed wound healing [1,2,3]. One study showed that skin injuries are the most common medical events in a space mission, including dry and itchy skin that makes it more likely to scratch and irritate [4]. These suggest that under the conditions of microgravity, the normal physiological characteristics of the skin are affected and becomes more vulnerable. Dermal fibroblasts are critical in supporting skin-repairing [5]. It has been found that BMSCs could differentiate into dermal fibroblasts to participate in wound repairing after skin injury [7,8]. Little is known about the effect of microgravity conditions on the differentiation process and the involved molecular mechanism
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