RepSox effectively promotes the induced differentiation of sheep fibroblasts into adipocytes via the inhibition of the TGF-beta 1/Smad pathway

文献类型： 外文期刊

第一作者： Guo, Yu

作者： Guo, Yu;Zhu, Huan;Ma, Caiyun;Sun, Tingting;Wang, Yuanyuan;Wang, Chunjing;Liu, Changqing;Li, Xiangchen;Ma, Caiyun;Li, Yanan;Guan, Weijun;Li, Xiangchen

作者机构：

关键词： RepSox; adipogenic differentiation; fibroblasts; octamer-binding transcription factor 4; transforming growth factor-beta/Smad

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE （ 影响因子：4.101； 五年影响因子：4.084 ）

ISSN： 1107-3756

年卷期： 2021 年 48 卷 2 期

页码：

收录情况： SCI

摘要： Previous reports have demonstrated that RepSox can function as a replacement for cMyc and Sox2 in the reprogramming of cells into induced pluripotent stem cells (iPSCs), as well as increasing the levels of bone morphogenetic protein (BMP)-3 and inducing the phosphorylation of Smad1 in mouse embryonic stem cells. In the present study, it was demonstrated that RepSox caused the visible morphological transformation of sheep fibroblasts; however, no significant alterations in cell proliferation, apoptosis or chromosome aberrations were observed. Moreover, RepSox increased the plasticity of long-term cryopreserved sheep fibroblasts, and further promoted differentiation into adipocytes. RepSox treatment led to a notable decrease in the expression of components of the transforming growth factor (TGF)-beta signaling pathway, particularly Smad2/3 phosphorylation. RepSox also activated the BMP pathway, promoted the reprogramming of cells from fibroblasts into adipocytes and induced mesenchymal-epithelial transition. It is worth noting that RepSox notably increased the expression of octamer-binding transcription factor 4 and L-Myc, whereas Sox2 and Nanog expression were not detected. The results of high-throughput RNA sequencing revealed that the levels of differentially expressed genes (DEGs) involved in various metabolic processes were markedly upregulated in the RepSox-treated fibroblasts, while the DEGs in the majority of signaling pathways were markedly downregulated. On the whole, the present study demonstrates that RepSox can promote the plasticity of sheep fibroblasts and facilitates the differentiation of adipocytes via increasing BMP expression and inhibiting the activation of the TGF-beta signaling pathway.

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