title: Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm.
abstract: MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA.
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Jiao
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Biotechnology Institute, School of Environment and Chemical Engineering, Dalian Jiaotong University, Dalian 116028, China.
authors.forename: Da-Cheng
authors.identifier: 0000-0001-6589-4023
authors.initials: DC
authors.lastname: Hao
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Sun
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Jing
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Hai-Yang
authors.identifier: 0000-0002-2762-0002
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000072197:ADAM10 Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites; D004151:Dipeptides / Q000008:administration & dosage; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C555398:3-(formylhydroxyamino)-2-(3-phenyl-1-propyl)butanoic acid (2,2-dimethyl-1-methylcarbamoyl-1-propyl)amide; D004151:Dipeptides; D006877:Hydroxamic Acids; C555364:MIRN103 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D016372:RNA, Antisense; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse