| First Author | Belgardt BF | Year | 2015 |
| Journal | Nat Med | Volume | 21 |
| Issue | 6 | Pages | 619-27 |
| PubMed ID | 25985365 | Mgi Jnum | J:314874 |
| Mgi Id | MGI:6828783 | Doi | 10.1038/nm.3862 |
| Citation | Belgardt BF, et al. (2015) The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nat Med 21(6):619-27 |
| abstractText | Pancreatic beta cell death is a hallmark of type 1 (T1D) and type 2 (T2D) diabetes, but the molecular mechanisms underlying this aspect of diabetic pathology are poorly understood. Here we report that expression of the microRNA (miR)-200 family is strongly induced in islets of diabetic mice and that beta cell-specific overexpression of miR-200 in mice is sufficient to induce beta cell apoptosis and lethal T2D. Conversely, mir-200 ablation in mice reduces beta cell apoptosis and ameliorates T2D. We show that miR-200 negatively regulates a conserved anti-apoptotic and stress-resistance network that includes the essential beta cell chaperone Dnajc3 (also known as p58IPK) and the caspase inhibitor Xiap. We also observed that mir-200 dosage positively controls activation of the tumor suppressor Trp53 and thereby creates a pro-apoptotic gene-expression signature found in islets of diabetic mice. Consequently, miR-200-induced T2D is suppressed by interfering with the signaling of Trp53 and Bax, a proapoptotic member of the B cell lymphoma 2 protein family. Our results reveal a crucial role for the miR-200 family in beta cell survival and the pathophysiology of diabetes. |
