Nie, Li, Gao, Shi-jun, Zhao, Ya-nan, Masika, Jacob, Luo, Hong-yan, Hu, Xin-wu, Zhang, Liang-pin, Zeng, Ying, Hescheler, Juergen and Liang, Hua-min (2016). Thymosin beta 4 impeded murine stem cell proliferation with an intact cardiovascular differentiation. J. Huazhong Univ. Sci. Tech.-Med., 36 (3). S. 328 - 335. NEW YORK: SPRINGER. ISSN 1993-1352

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Abstract

Thymosin beta 4 (T beta 4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of T beta 4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that T beta 4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by T beta 4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by T beta 4 with upregulation of Tcf3 and constant beta-catenin. Under mESCs differentiation, T beta 4 treatment did not change the expression of cardiovascular cell markers alpha-MHC, PECAM, and alpha-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by T beta 4. In conclusion, T beta 4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, T beta 4 did not influence the in vitro cardiovascular differentiation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nie, LiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, Shi-junUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, Ya-nanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Masika, JacobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luo, Hong-yanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, Xin-wuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, Liang-pinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeng, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, Hua-minUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-273153
DOI: 10.1007/s11596-016-1587-6
Journal or Publication Title: J. Huazhong Univ. Sci. Tech.-Med.
Volume: 36
Number: 3
Page Range: S. 328 - 335
Date: 2016
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1993-1352
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SELF-RENEWAL; ES CELLS; CLINICAL-APPLICATIONS; HAIR-GROWTH; PLURIPOTENCY; ACTIVATION; MIGRATION; PATHWAYS; BETA(4); REPAIRMultiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27315

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