{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:30:24Z","timestamp":1792762224686,"version":"4.5.0"},"reference-count":55,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:p> Idiopathic pulmonary fibrosis (IPF) is characterized by the relentless spread of fibroblasts from scarred alveoli into adjacent alveolar units, resulting in progressive hypoxia and death by asphyxiation. Although hypoxia is a prominent clinical feature of IPF, the role of hypoxia as a driver of the progressive fibrotic nature of the disease has not been explored. Here, we demonstrate that hypoxia robustly stimulates the proliferation of IPF fibroblasts. We found that miR-210 expression markedly increases in IPF fibroblasts in response to hypoxia and that knockdown of miR-210 decreases hypoxia-induced IPF fibroblast proliferation. Silencing hypoxia-inducible factor (HIF)-2\u03b1 inhibits the hypoxia-mediated increase in miR-210 expression and blocks IPF fibroblast proliferation, indicating that HIF-2\u03b1 is upstream of miR-210. We demonstrate that the miR-210 downstream target MNT is repressed in hypoxic IPF fibroblasts and that knockdown of miR-210 increases MNT expression. Overexpression of MNT inhibits hypoxia-induced IPF fibroblast proliferation. Together, these data indicate that hypoxia potently stimulates miR-210 expression via HIF-2\u03b1, and high miR-210 expression drives fibroblast proliferation by repressing the c-myc inhibitor, MNT. In situ analysis of IPF lung tissue demonstrates miR-210 expression in a similar distribution with HIF-2\u03b1 and the hypoxic marker carbonic anhydrase-IX in cells within the IPF fibrotic reticulum. Our results raise the possibility that a pathological feed-forward loop exists in the IPF lung, in which hypoxia promotes IPF fibroblast proliferation via stimulation of miR-210 expression, which in turn worsens hypoxia. <\/jats:p>","DOI":"10.1152\/ajplung.00069.2014","type":"journal-article","created":{"date-parts":[[2014,6,21]],"date-time":"2014-06-21T02:37:55Z","timestamp":1403318275000},"page":"L283-L294","source":"Crossref","is-referenced-by-count":84,"title":["miR-210 promotes IPF fibroblast proliferation in response to hypoxia"],"prefix":"10.1152","volume":"307","author":[{"given":"Vidya","family":"Bodempudi","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polla","family":"Hergert","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajahat","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Kahm","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Bitterman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Henke","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.ats3-00"},{"key":"B2","first-page":"443","volume":"122","author":"Basset F","year":"1986","journal-title":"Am J Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001653107"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040970327"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1755"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01258.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.6.11006"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116052"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200602-205OC"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.150.4.7921471"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.14.2120"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(03)00012-0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800731200"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.052779"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(68)90361-3"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/186315a0"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-488OC"},{"key":"B18","first-page":"171","volume":"126","author":"Fukuda Y","year":"1987","journal-title":"Am J Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.7.2.5297"},{"key":"B20","first-page":"454","volume-title":"Textbook of Medical Physiology","author":"Guyton AC","year":"2000","edition":"10"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00192-09"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrc704"},{"key":"B23","first-page":"3810","volume":"117","author":"Higgins DF","year":"2007","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.928424"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R200030200"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.09.006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21690"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200501-006AC"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201201-0084OC"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0314OC"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.6.1693"},{"key":"B32","first-page":"1257","volume":"138","author":"Kuhn C","year":"1991","journal-title":"Am J Pathol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003220"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2003.tb02668.x"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.03.018"},{"key":"B36","first-page":"6394","volume":"61","author":"Loncaster JA","year":"2001","journal-title":"Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.153.5.8630600"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90356.2008"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.56"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.259325"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01080.2010"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2005.08.003"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2004.04.003"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021253"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904606106"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1667\/RR1816.1"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200602-163OC"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-134-2-200101160-00015"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.62"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.11.132"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080001"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091117"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.034"},{"key":"B54","first-page":"A3559","volume":"183","author":"Yang IV","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.17.9387"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00069.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:44:36Z","timestamp":1567975476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00069.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,15]]},"references-count":55,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8,15]]}},"alternative-id":["10.1152\/ajplung.00069.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00069.2014","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,15]]}}}