Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARα.

Autor:	Chen Q; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Qiu F; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Zhou K; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Matlock HG; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Takahashi Y; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK yusuke-takahashi@ouhsc.edu.; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Rajala RVS; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Yang Y; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China., Moran E; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Department of Ophthalmology, Boston Children's Hospital, Boston, MA., Ma JX; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2017 Jun; Vol. 66 (6), pp. 1671-1682. Date of Electronic Publication: 2017 Mar 07.
DOI:	10.2337/db16-1246
Abstrakt:	Fenofibrate, a specific agonist of peroxisome proliferator-activated receptor-α (PPARα), displays robust therapeutic effects on diabetic retinopathy (DR) in patients with type 2 diabetes. Our recent studies have shown that PPARα is downregulated in the diabetic retina, which contributes to the pathogenesis of DR. However, the mechanism for diabetes-induced downregulation of PPARα remains unknown. We investigated the role of microRNA-21 ( miR-21 ) in regulating PPARα in DR. miR-21 was overexpressed, while PPARα 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 PPARα by inhibiting its mRNA translation. Knockout of miR-21 prevented the decrease of PPARα, alleviated microvascular damage, ameliorated inflammation, and reduced cell apoptosis in the retina of db/db mice. Intravitreal injection of miR-21 inhibitor attenuated PPARα downregulation and ameliorated retinal inflammation in db/db mice. Further, retinal miR-21 levels were increased, while PPARα levels were decreased in oxygen-induced retinopathy (OIR). Knockout of miR-21 prevented PPARα 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 PPARα downregulation in DR. Targeting miR-21 may represent a novel therapeutic strategy for DR. (© 2017 by the American Diabetes Association.)
Databáze:	MEDLINE
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