Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro.
Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro.
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DOI：
10.1097/md.0000000000007607
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发表时间：
2017-07
期刊：
影响因子：
1.6
通讯作者：
Tong X
中科院分区：
文献类型：
--
作者：
Ai G;Shao X;Meng M;Song L;Qiu J;Wu Y;Zhou J;Cheng J;Tong X
本研究旨在探讨表皮生长因子（epidermal growth factor， EGF）在脂肪干细胞（adipose stem cells， ASC）重复传代过程中对其增殖分化的影响，并探讨其潜在的信号通路。结果显示，与未处理的ASCs相比，经EGF处理的ASCs的Ki67阳性率保持在较高水平，G0/G1期ASCs数量明显减少，但G2/M期和S期ASCs数量明显增加，表明EGF在增殖期产生更多的ASCs。与EGF处理后的ASCs相比，未处理EGF的ASCs的成脂能力受到损害，但未观察到显著差异。EGF治疗后，ASC的成骨和成软骨能力显著增强，表明EGF可以维持ASC的分化能力。基因集富集分析显示，EGF上调上皮间充质转化和G2/M检查点信号通路分子的表达。GeneMANIA数据库分析表明EGF和STAT之间存在网络相互作用。EGF受体（EGFR）抑制剂和STAT3抑制剂被独立用于验证这两种途径在这些作用中的作用。抑制EGFR或STAT3后，ASCs的增殖明显受到抑制，Western blotting显示EGF能够显著增加EGFR和STAT3的表达。这些发现表明，EGF不仅促进ASCs的增殖和延缓其衰老，而且维持ASCs的分化能力，这与EGF诱导的STAT信号通路的激活有关。
This study aimed to investigate the effects of epidermal growth factor (EGF) on the proliferation and differentiation of adipose stem cells (ASC) during the repeated passaging and probe the underlying signal pathway. Results showed that the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1 phase reduced significantly, but ASCs in G2/M phase and S phase increased markedly in ASCs treated with EGF when compared with ASCs without EGF treatment, indicating that EGF made more ASCs in proliferation phase. The adipogenic capability of ASCs without EGF was compromised when compared with that of ASCs after EGF treatment, although significant difference was not observed. The osteogenic and chondrogenic potencies increased significantly in ASC with EGF treatment indicating EGF could maintain differentiative capacity of ASCs. Gene Set Enrichment Analysis showed EGF upregulated the expression of molecules in the epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA database analysis indicated the network interaction between EGF and STAT. EGF receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate the role of both pathways in these effects. After inhibition of EGFR or STAT3, the proliferation of ASCs was significantly inhibited, and Western blotting showed EGF was able to markedly increase the expression of EGFR and STAT3. These findings suggest EGF not only promotes the proliferation of ASCs and delays their senescence, but also maintains the differentiation potency of ASCs, which are related to the EGF-induced activation of STAT signal pathway.