| First Author | Zhao J | Year | 2014 |
| Journal | J Cell Mol Med | Volume | 18 |
| Issue | 8 | Pages | 1562-70 |
| PubMed ID | 24974728 | Mgi Jnum | J:233559 |
| Mgi Id | MGI:5784966 | Doi | 10.1111/jcmm.12339 |
| Citation | Zhao J, et al. (2014) beta-arrestin2/miR-155/GSK3beta regulates transition of 5'-azacytizine-induced Sca-1-positive cells to cardiomyocytes. J Cell Mol Med 18(8):1562-70 |
| abstractText | 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. beta-arrestin2 is an important scaffold protein and highly expressed in the heart. To explore the function of beta-arrestin2 in Sca-1+ CSC differentiation, we used beta-arrestin2-knockout mice and overexpression strategies. Real-time PCR revealed that beta-arrestin2 promoted 5'-azacytizine-induced Sca-1+ CSC differentiation in vitro. Because the microRNA 155 (miR-155) may regulate beta-arrestin2 expression, we detected its role and relationship with beta-arrestin2 and glycogen synthase kinase 3 (GSK3beta), another probable target of miR-155. Real-time PCR revealed that miR-155, inhibited by beta-arrestin2, impaired 5'-azacytizine-induced Sca-1+ CSC differentiation. On luciferase report assay, miR-155 could inhibit the activity of beta-arrestin2 and GSK3beta, which suggests a loop pathway between miR-155 and beta-arrestin2. Furthermore, beta-arrestin2-knockout inhibited the activity of GSK3beta. Akt, the upstream inhibitor of GSK3beta, was inhibited in beta-arrestin2-Knockout mice, so the activity of GSK3beta was regulated by beta-arrestin2 not Akt. We transplanted Sca-1+ CSCs from beta-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 beta-arrestin2 agreed with decreased phosphorylation of AKT and increased phophorylation of GSK3beta, similar to in vitro findings. The beta-arrestin2/miR-155/GSK3beta pathway may be a new mechanism with implications for treatment of heart disease. |
