| First Author | Chen Q | Year | 2017 |
| Journal | Diabetes | Volume | 66 |
| Issue | 6 | Pages | 1671-1682 |
| PubMed ID | 28270521 | Mgi Jnum | J:246071 |
| Mgi Id | MGI:5922605 | Doi | 10.2337/db16-1246 |
| Citation | Chen Q, et al. (2017) Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARalpha. Diabetes 66(6):1671-1682 |
| abstractText | Fenofibrate, a specific agonist of peroxisome proliferator-activated receptor-alpha (PPARalpha), displays robust therapeutic effects on diabetic retinopathy (DR) in patients with type 2 diabetes. Our recent studies have shown that PPARalpha is downregulated in the diabetic retina, which contributes to the pathogenesis of DR. However, the mechanism for diabetes-induced downregulation of PPARalpha remains unknown. We investigated the role of microRNA-21 (miR-21) in regulating PPARalpha in DR. miR-21 was overexpressed, while PPARalpha levels were decreased in the retina of db/db mice, a model of type 2 diabetes. Such alterations were also observed in palmitate-treated retinal endothelial cells. miR-21 targeted PPARalpha by inhibiting its mRNA translation. Knockout of miR-21 prevented the decrease of PPARalpha, alleviated microvascular damage, ameliorated inflammation, and reduced cell apoptosis in the retina of db/db mice. Intravitreal injection of miR-21 inhibitor attenuated PPARalpha downregulation and ameliorated retinal inflammation in db/db mice. Further, retinal miR-21 levels were increased, while PPARalpha levels were decreased in oxygen-induced retinopathy (OIR). Knockout of miR-21 prevented PPARalpha downregulation and ameliorated retinal neovascularization and inflammation in OIR retinas. In conclusion, diabetes-induced overexpression of miR-21 in the retina is at least partly responsible for PPARalpha downregulation in DR. Targeting miR-21 may represent a novel therapeutic strategy for DR. |
