{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T10:13:43Z","timestamp":1771064023360,"version":"3.50.1"},"reference-count":95,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Disease Markers"],"published-print":{"date-parts":[[2021,12,21]]},"abstract":"<jats:p>Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-\u03b1), 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<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:msup>\n                           <a:mrow\/>\n                           <a:mrow>\n                              <a:mo>\u2032<\/a:mo>\n                           <\/a:mrow>\n                        <\/a:msup>\n                     <\/a:math>\n                  <\/jats:inline-formula>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-1\u03b1 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-1\u03b1, whereas B-cell lymphoma 2(Bcl2), a HIF-1\u03b1, 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-1\u03b1 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.<\/jats:p>","DOI":"10.1155\/2021\/4933194","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:05:24Z","timestamp":1640135124000},"page":"1-14","source":"Crossref","is-referenced-by-count":13,"title":["MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis"],"prefix":"10.1155","volume":"2021","author":[{"given":"Jinxue","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Wei","sequence":"additional","affiliation":[{"name":"Gulliver High School, Miami, FL 33156, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianqin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Medicine Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen 529030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Webster","sequence":"additional","affiliation":[{"name":"Integene International, LLC, Miami, FL 33137, USA"},{"name":"Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Everglades Biopharma, LLC, Houston, TX 77030, 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Surgery, Youjiang Medical University for Nationalities, Chengxiang Rd, Baise, Guangxi 533000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusheng","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou 510080, China"},{"name":"Department of Cardiology, Guangdong Cardiovascular Institute and Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuyu","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou 510080, China"},{"name":"Department of Cardiology, Guangdong Cardiovascular Institute and Shantou University Medical College, Shantou 515041, 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