Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro

• Published in: Medicine (Baltimore) Vol. 96; no. 30; p. e7607
• Main Authors: Ai, Guihai, Shao, Xiaowen, Meng, Meng, Song, Liwen, Qiu, Jin, Wu, Yi, Zhou, Jianhong, Cheng, Jiajing, Tong, Xiaowen
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 01.07.2017
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis - drug effects; Adipogenesis - physiology; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - physiology; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cells, Cultured; Cellular Senescence - drug effects; Cellular Senescence - physiology; Chondrogenesis - drug effects; Chondrogenesis - physiology; Epidermal Growth Factor - administration & dosage; Epidermal Growth Factor - metabolism; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; Growth Substances - administration & dosage; Growth Substances - metabolism; Humans; Multipotent Stem Cells - drug effects; Multipotent Stem Cells - metabolism; Observational Study; Osteogenesis - drug effects; Osteogenesis - physiology; Signal Transduction; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/md.0000000000007607

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.