Document Type
Article
Publication Date
1-1-2014
Description
Stem-cell antigen 1-positive (Sca-1+) cardiac stem cells (CSCs), a vital kind of CSCs in humans, promote cardiac repair in vivo and can differentiate to cardiomyocytes with 5'-azacytizine treatment in vitro. However, the underlying molecular mechanisms are unknown. b-arrestin2 is an important scaffold protein and highly expressed in the heart. To explore the function of b-arrestin2 in Sca-1+ CSC differentiation, we used b-arrestin2-knockout mice and overexpression strategies. Real-time PCR revealed that b-arrestin2 promoted 5'-azacytizine-induced Sca-1+ CSC differentiation in vitro. Because the microRNA 155 (miR-155) may regulate b-arrestin2 expression, we detected its role and relationship with b-arrestin2 and glycogen synthase kinase 3 (GSK3β), another probable target of miR-155. Real-time PCR revealed that miR-155, inhibited by b-arrestin2, impaired 5'-azacytizine-induced Sca-1+ CSC differentiation. On luciferase report assay, miR-155 could inhibit the activity of b-arrestin2 and GSK3β, which suggests a loop pathway between miR-155 and b-arrestin2. Furthermore, b-arrestin2-knockout inhibited the activity of GSK3β. Akt, the upstream inhibitor of GSK3β, was inhibited in b-arrestin2-Knockout mice, so the activity of GSK3β was regulated by b-arrestin2 not Akt. We transplanted Sca-1+ CSCs from b-arrestin2-knockout mice to mice with myocardial infarction and found similar protective functions as in wild-type mice but impaired arterial elastance. Furthermore, low level of b-arrestin2 agreed with decreased phosphorylation of AKT and increased phophorylation of GSK3β, similar to in vitro findings. The β-arrestin2/miR-155/GSK3β pathway may be a new mechanism with implications for treatment of heart disease.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Zhao, Jing; Feng, Yimin; Yan, Hui; Chen, Yangchao; Wang, Jinlan; Chua, Balvin; Stuart, Charles; and Yin, Deling. 2014. β-arrestin2/miR-155/GSK3β Regulates Transition of 5'-Azacytizine-Induced Sca-1-Positive Cells to Cardiomyocytes. Journal of Cellular and Molecular Medicine. Vol.18(8). 1562-1570. https://doi.org/10.1111/jcmm.12339 PMID: 24974728 ISSN: 1582-1838
Copyright Statement
a 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.