{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:35:13Z","timestamp":1791995713344,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973553"],"award-info":[{"award-number":["81973553"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Calpain\u20101, a calcium\u2010activated neutral cysteine proteases, has been reported to be involved in the formation of pulmonary hypertension. HIF\u20101\u03b1, an oxygen\u2010sensitive transcription factor, has been reported to activate genes involved in cell proliferation and extracellular matrix recombination. This study was designed to investigate the effect of calpain\u20101 in hypoxic pulmonary hypertension (HPH) and to explore whether there is a relationship between calpain\u20101 and HIF\u20101\u03b1 in this disease. In the hypoxia\u2010induced model of HPH, we found that hypoxia resulted in increased right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodelling and collagen deposition in lung tissues of mice. The levels of calpain\u20101 and HIF\u20101\u03b1 were up\u2010regulated in the lung tissues of hypoxia\u2010treated mice and pulmonary arterial smooth muscle cells (PASMCs). Knock\u2010out of calpain\u20101 restrained haemodynamic and histological changes induced by chronic hypoxia in mice, and inhibition of calpain\u20101 also repressed the abnormal proliferation and migration of PASMCs. Besides, knock\u2010out or inhibition of calpain\u20101 suppressed hypoxia\u2010induced expression of HIF\u20101\u03b1, VEGF, PCNA, TGF\u2010\u03b21, MMP2 and collagen I in vivo and in vitro. While inhibition of HIF\u20101\u03b1 abolished the above effects of calpain\u20101. Furthermore, we found that calpain\u20101 mediates the expression of HIF\u20101\u03b1 through NF\u2010\u03baB (P65) under hypoxia conditions. In conclusion, our results suggest that calpain\u20101 plays a pivotal role in hypoxia\u2010induced pulmonary vascular remodelling and fibrosis through HIF\u20101\u03b1, providing a better understanding of the pathogenesis of HPH.<\/jats:p>","DOI":"10.1111\/jcmm.17295","type":"journal-article","created":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T06:41:36Z","timestamp":1648881696000},"page":"2819-2830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Calpain\u20101 mediates vascular remodelling and fibrosis via HIF\u20101\u03b1 in hypoxia\u2010induced pulmonary hypertension"],"prefix":"10.1111","volume":"26","author":[{"given":"Haiyan","family":"Deng","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province Jinzhou Medical University  Jinzhou 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