{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:31:58Z","timestamp":1782401518617,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pulmonary arterial hypertension (PAH) is a devastating disease, and no effective treatments are available. Hypoxia-induced pulmonary artery remodeling, including smooth muscle cell proliferation, contributes to PAH, but the exact mechanisms underlying this abnormal process are largely undefined. The forkhead box M1 (FoxM1) transcription factor regulates cancer cell growth by modulating gene expression critical for cell cycle progression. Here, we report for the first time, to the best of our knowledge, a novel function of FoxM1 in the hypoxia-stimulated proliferation of human pulmonary artery smooth muscle cells (HPASMCs). Exposure to hypoxia caused a marked up-regulation of FoxM1 gene expression, mainly at the transcription level, and this induction correlated with HPASMC cell proliferation. The knockdown of FoxM1 inhibited the hypoxia-stimulated proliferation of HPASMCs. We found that the knockdown of HIF-2\u03b1, but not HIF-1\u03b1, diminished FoxM1 induction in response to hypoxia. However, the knockdown of FoxM1 did not alter expression levels of HIF-2\u03b1 or HIF-1\u03b1, suggesting that HIF-2\u03b1 is an upstream regulator of FoxM1. Furthermore, the knockdown of FoxM1 prevented the hypoxia-induced expression of aurora A kinase and cyclin D1. Collectively, our results suggest that hypoxia induces FoxM1 gene expression in an HIF-2\u03b1\u2013dependent pathway, thereby promoting HPASMC proliferation.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0128oc","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T23:01:42Z","timestamp":1319756502000},"page":"431-436","source":"Crossref","is-referenced-by-count":53,"title":["Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation Is Controlled by Forkhead Box M1"],"prefix":"10.1093","volume":"46","author":[{"given":"Aarti","family":"Raghavan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, and"},{"name":"Department of Pediatrics, Children's Hospital of the University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Christina F.","family":"Ibe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"},{"name":"Department of Pediatrics, Children's Hospital of the University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramaswamy","family":"Ramchandran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini","family":"Racherla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Raychaudhuri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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