RepSox effectively promotes the induced differentiation of sheep fibroblasts into adipocytes via the inhibition of the TGF‑β1/Smad pathway
| Autor: | Sun Tingting, Weijun Guan, Huan Zhu, Yuanyuan Wang, Yanan Li, Changqing Liu, Yu Guo, Xiangchen Li, Caiyun Ma, Chunjing Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Homeobox protein NANOG
Male Pyridines Gene Expression Apoptosis Smad Proteins SMAD Bone Morphogenetic Protein 4 Bone morphogenetic protein octamer-binding transcription factor 4 Transforming Growth Factor beta1 SOX2 Genetics Adipocytes Animals RNA-Seq Phosphorylation Induced pluripotent stem cell Bone Morphogenetic Protein Receptors Type I Cells Cultured Cell Proliferation RepSox Sheep Chemistry Cell Differentiation Articles General Medicine Fibroblasts Embryonic stem cell Cell biology transforming growth factor-β/Smad Pyrazoles adipogenic differentiation Reprogramming Transforming growth factor Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X |
| Popis: | 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)-β 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-β signaling pathway. |
| Databáze: | OpenAIRE |
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