title: MiR-181c restrains nitration stress of endothelial cells in diabetic db/db mice through inhibiting the expression of FoxO1.
abstract: Endothelial dysfunction played an important role in the progression of diabetes mellitus (DM). miR-181c has been implicated in many diseases, including DM. However, the molecular mechanisms of miR-181c regulate this process remained poorly understood. Healthy ICR mice were divided into control group (n = 10) and db/db DM group (n = 10). The expression of miR-181c and FoxO1 were both investigated in diabetic db/db mice or high glucose-induced endothelial cells (MAECs and END-D). Here we found that down-regulation of miR-181c and the activation of FoxO1/iNOS were observed in mice and endothelial cells. Furthermore, we verified that miR-181c directly targeted and inhibited FoxO1 gene expression by targeting its 3'-UTR through luciferase reporter assay. Knockdown of FoxO1 reversed the up-regulation of iNOS, nitrotyrosine and the down-regulation of p-eNOSSer1177/eNOS in high glucose (30 mM)-induced MAECs cells. In addition, over-expression of miR-181c could reverse the enhanced nitration stress induced by high glucose, while this effect could be attenuated by pcDNA-FoxO1 in MAECs. These results shown that miR-181c attenuated nitration stress through regulating FoxO1 expression and affecting endothelial cell function, which offering a new target for the development of preventive or therapeutic agents against DM.
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, China. Electronic address: shandongyeyes@126.com.
authors.forename: Shandong
authors.initials: S
authors.lastname: Ye
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D000071161:Forkhead Box Protein O1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015538:Nitrosation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; D035683:MicroRNAs; C529100:mirn181 microRNA, mouse; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005947:Glucose
keywords: Diabetes mellitus; Endothelial cell; FoxO1; MiR-181c; Nitration stress