title: Exendin-4 promotes proliferation of adipose-derived stem cells through ERK and JNK signaling pathways.
abstract: Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of exendin-4 (Ex-4), a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD90 and CD29 but negative for CD31, CD34, and CD45. Ex-4 (0-50 nM) treatment increased ADSC proliferation in a dose-dependent manner but had no effects on stem cell markers of ADSCs. Moreover, we found that Ex-4 treatment elevated the phosphorylation levels of the JNK and ERK signaling pathways. Furthermore, utilization of Ex-4 also promoted cyclin D1 and cyclin E protein expression, which was accompanied by more Edu(+) cells and a higher percentage of cells in the S-phase of the cell cycle after Ex-4 treatment. In parallel, the application of inhibitors SP600125 and PD98059, inhibitors of the JNK and ERK signaling pathways, respectively, not only reversed such effects of Ex-4 on JNK and ERK but also resulted in lower percentages of S-phase cells and fewer numbers of Edu(+) cells. In summary, Ex-4 has no effects on stem cell markers in ADSCs but promotes ADSC growth via JNK and ERK signaling pathways.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Beijing Cancer Hospital, Beijing, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Emergency, Jishuitan Hospital, Tianjin, China.
authors.forename: Baichuan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
authors.forename: Shunyin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, #28 Fuxing Rd, Beijing, 100853, China. yundaic@163.com.
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D000077270:Exenatide; D005434:Flow Cytometry; D019012:Integrin beta1 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D014688:Venoms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; D019012:Integrin beta1; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018800:Thy-1 Antigens; D014688:Venoms; D000077270:Exenatide; D017493:Leukocyte Common Antigens
keywords: Adipose-derived stem cells; Exendin-4; JNK/ERK signaling pathway; Proliferation