{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:05:40Z","timestamp":1790856340777,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["HL133474"],"award-info":[{"award-number":["HL133474"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["HL144909"],"award-info":[{"award-number":["HL144909"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is characterized by endothelial dysfunction, uncontrolled proliferation and migration of pulmonary arterial endothelial cells leading to increased pulmonary vascular resistance resulting in great morbidity and poor survival. Bone morphogenetic protein receptor II (BMPR2) plays an important role in the pathogenesis of PAH as the most common genetic mutation. Non-muscle myosin light chain kinase (nmMLCK) is an essential component of the cellular cytoskeleton and recent studies have shown that increased nmMLCK activity regulates biological processes in various pulmonary diseases such as asthma and acute lung injury. In this study, we aimed to discover the role of nmMLCK in the proliferation and migration of pulmonary arterial endothelial cells (HPAECs) in the pathogenesis of PAH. We used two cellular models relevant to the pathobiology of PAH including BMPR2 silenced and vascular endothelial growth factor (VEGF) stimulated HPAECs. Both models demonstrated an increase in nmMLCK activity along with a robust increase in cellular proliferation, inflammation, and cellular migration. The upregulated nmMLCK activity was also associated with increased ERK expression pointing towards a potential integral cytoplasmic interaction. Mechanistically, we confirmed that when nmMLCK is inhibited by MLCK selective inhibitor (ML-7), proliferation and migration are attenuated. In conclusion, our results demonstrate that nmMLCK upregulation in association with increased ERK expression may contribute to the pathogenesis of PAHby stimulating cellular proliferation and migration.<\/jats:p>","DOI":"10.3390\/ijms232113641","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T10:53:06Z","timestamp":1667904786000},"page":"13641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Non-Muscle MLCK Contributes to Endothelial Cell Hyper-Proliferation through the ERK Pathway as a Mechanism for Vascular Remodeling in Pulmonary Hypertension"],"prefix":"10.3390","volume":"23","author":[{"given":"Mariam","family":"Anis","sequence":"first","affiliation":[{"name":"Northwestern Medical Group, Lake Forest, IL 60045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-6134","authenticated-orcid":false,"given":"Janae","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Halstrom","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noman","family":"Baig","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cat","family":"Humpal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regaina","family":"Demeritte","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Epshtein","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin R.","family":"Fraidenburg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D42","DOI":"10.1016\/j.jacc.2013.10.032","article-title":"Definitions and diagnosis of pulmonary hypertension","volume":"62","author":"Hoeper","year":"2013","journal-title":"J. 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