| First Author | Zhou H | Year | 2022 |
| Journal | FASEB J | Volume | 36 |
| Issue | 6 | Pages | e22353 |
| PubMed ID | 35593587 | Mgi Jnum | J:359022 |
| Mgi Id | MGI:7344277 | Doi | 10.1096/fj.202200046R |
| Citation | Zhou H, et al. (2022) miR-181b regulates vascular endothelial aging by modulating an MAP3K3 signaling pathway. FASEB J 36(6):e22353 |
| abstractText | Endothelial cell (EC) aging plays a vital role in the pathogenesis of cardiovascular disease (CVD). MicroRNAs have emerged as crucial regulators of target gene expression by inhibiting mRNA translation and/or promoting mRNA degradation. We identify an aging-related and oxidative stress-responsive microRNA, miR-181b, that inhibits endothelial cell apoptosis and senescence. In gain- or loss-of-function studies, miR-181b regulated the expression of key apoptosis markers (Bcl2, Bax, cleaved-Caspase3) and senescence markers (p16, p21, gammaH2AX) and the ratio of apoptotic cells (TUNEL-positive) and senescent cells (SA-betagal-positive) in H2 O2 -induced ECs. Mechanistically, miR-181b targets MAP3K3 and modulates a MAP3K3/MKK/MAPK signaling pathway. MAP3K3 knockdown recapitulated the phenotype of miR-181b overexpression and miR-181b was dependent on MAP3K3 for regulating EC apoptosis and senescence. In vivo, miR-181b expression showed a negative correlation with increasing age in the mouse aorta. Endothelial-specific deficiency of miR-181a2b2 increased the target MAP3K3, markers of vascular senescence (p16, p21), and DNA double-strand breaks (gammaH2AX) in the aorta of aged mice. Collectively, this study unveils an important role of miR-181b in regulating vascular endothelial aging via an MAP3K3-MAPK signaling pathway, providing new potential therapeutic targets for antiaging therapy in CVD. |
