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MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis.
Liu, Jinxue; Wei, Eileen; Wei, Jianqin; Zhou, Wei; Webster, Keith A; Zhang, Bin; Li, Dong; Zhang, Gaoxing; Wei, Yidong; Long, Yusheng; Qi, Xiuyu; Zhang, Qianhuan; Xu, Dingli.
Afiliação
  • Liu J; Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Wei E; Gulliver High School, Miami, FL 33156, USA.
  • Wei J; Department of Medicine Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
  • Zhou W; Department of Ophthalmology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529030, China.
  • Webster KA; Integene International, LLC, Miami, FL 33137, USA.
  • Zhang B; Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Li D; Everglades Biopharma, LLC, Houston, TX 77030, USA.
  • Zhang G; Department of Cardiology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529030, China.
  • Wei Y; Department of Intensive Care Unit and Clinical Experimental Center, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529030, China.
  • Long Y; Department of Cardiology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529030, China.
  • Qi X; Department of Surgery, Youjiang Medical University for Nationalities, Chengxiang Rd, Baise, Guangxi 533000, China.
  • Zhang Q; Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou 510080, China.
  • Xu D; Department of Cardiology, Guangdong Cardiovascular Institute and Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Dis Markers ; 2021: 4933194, 2021.
Article em En | MEDLINE | ID: mdl-34970357
Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-α), and high-mobility group box-1 (HMGB1) contributes to the regulation of inflammation and angiogenesis in multiple physiological and pathophysiological settings. Here, we present evidence of an overriding role for miR-126 in the regulation of HMGB1 and its downstream proinflammatory effectors in endothelial cells subjected to hypoxia with concurrent acidosis (H/A). Methods. Primary mouse endothelial cells (PMEC) were exposed to hypoxia or H/A to simulate short or chronic low-flow ischemia, respectively. RT-qPCR quantified mRNA transcripts, and proteins were measured by western blot. ROS were quantified by fluorogenic ELISA and luciferase reporter assays employed to confirm an active miR-126 target in the HMGB1 3'UTR. Results. Enhanced expression of miR-126 in PMECs cultured under neutral hypoxia was suppressed under H/A, whereas the HMGB1 expression increased sequentially under both conditions. Enhanced expression of HMGB1 and downstream inflammation markers was blocked by the premiR-126 overexpression and optimized by antagomiR. Compared with neutral hypoxia, H/A suppressed the HIF-1α expression independently of miR-126. The results show that HMGB1 and downstream effectors are optimally induced by H/A relative to neutral hypoxia via crosstalk between hypoxia signaling, miR-126, and HIF-1α, whereas B-cell lymphoma 2(Bcl2), a HIF-1α, and miR-126 regulated gene expressed optimally under neutral hypoxia. Conclusion. Inflammatory responses of ECs to H/A are dynamically regulated by the combined actions of hypoxia, miR-126, and HIF-1α on the master regulator HMGB1. The findings may be relevant to vascular diseases including atherosclerotic occlusion and interiors of plaque where coexisting hypoxia and acidosis promote inflammation as a defining etiology.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Hipóxia Celular / Proteína HMGB1 / MicroRNAs / Células Endoteliais / Inflamação Limite: Animals Idioma: En Revista: Dis Markers Assunto da revista: BIOQUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Hipóxia Celular / Proteína HMGB1 / MicroRNAs / Células Endoteliais / Inflamação Limite: Animals Idioma: En Revista: Dis Markers Assunto da revista: BIOQUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China