title: Role of miR-124 and miR-141 in the regulation of vascular reactivity and the relationship to RhoA and Rac1 after hemorrhage and hypoxia.
abstract: Recent studies show that hypoxia can alter expression levels of microRNAs (miRNAs). Whether hypoxia or hemorrhage-induced vascular hyporeactivity is related to miRNAs and the underlying mechanisms of this process is not clear. Using hypoxia-treated superior mesenteric arteries (SMAs) and vascular smooth muscle cells (VSMCs) of rats that underwent hemorrhage, we observed the regulatory effects of miR-124/miR-141 on vascular reactivity, the relationship of these miRNAs to RhoA and Rac1, and the mutual regulation of miR-124 and miR-141. The contractile responses of SMAs and VSMCs showed an increase in early stages and a decrease in late stages of hypoxia and hemorrhage. Forty-five miRNAs appeared to have been significantly changed in SMAs after hypoxia, and miR-124 and miR-141 underwent the most change. Overexpressed miR-124 or miR-141 and their antisenses appeared to alter both vascular reactivity and expression of the proteins RhoA and Rac1 after hypoxia. miR-124 inhibited Rac1 by acting at the Rac1 mRNA 3'-untranslated region (UTR), but it led to an increase in RhoA by inhibiting miR-141. miR-141 inhibited RhoA by acting at the RhoA mRNA 3'-UTR, but it led to an increase in Rac1 by inhibiting miR-124. Further study found that miR-124 inhibited miR-141 via transcription factor early growth response gene-1 (Egr-1), whereas miR-141 inhibited miR-124 via transcription of nuclear factor erythroid 2-related factor 2 (Nrf-2). These results suggest that miR-124 and miR-141 participate in the regulation of vascular reactivity after hypoxia and hemorrhage by regulating expression of the RhoA and Rac1 proteins, and in doing so, miR-124 and miR-141 are mutually regulated. These findings provide potential targets for restoring vascular function as part of the treatment protocol for hemorrhagic shock and some other critical illness.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Liangming
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Jiatao
authors.initials: J
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China lt200132@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D019175:DNA Methylation; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005260:Female; D000860:Hypoxia / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D051381:Rats; D012771:Shock, Hemorrhagic / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; C570644:Mirn141 microRNA, rat; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Rac1; RhoA; miR-124; miR-141; vascular contraction