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Bortezomib (BTZ) is the first Food and Drug Administration (FDA)\u2010approved proteasome inhibitor for multiple myeloma treatment. Recently, there is emerging evidence showing its effect on reversing PAH, although its mechanisms are not well understood. In this study, anti\u2010proliferative and anti\u2010migratory effects of BTZ on PASMCs were first examined by different inducers such as fetal bovine serum (FBS), angiotensin II (Ang II) and platelet\u2010derived growth factor (PDGF)\u2010BB, while potential mechanisms including cellular reactive oxygen species (ROS) and mitochondrial ROS were then investigated; finally, signal transduction of ERK and Akt was examined. Our results showed that BTZ attenuated FBS\u2010, Ang II\u2010 and PDGF\u2010BB\u2010induced proliferation and migration, with associated decreased cellular ROS production and mitochondrial ROS production. In addition, the phosphorylation of ERK and Akt induced by Ang II and PDGF\u2010BB was also inhibited by BTZ treatment. This study indicates that BTZ can prevent proliferation and migration of PASMCs, which are possibly mediated by decreased ROS production and down\u2010regulation of ERK and Akt. Thus, proteasome inhibition can be a novel pharmacological target in the management of PAH.<\/jats:p>","DOI":"10.1002\/kjm2.12835","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T10:30:21Z","timestamp":1714386621000},"page":"542-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteasome inhibitor bortezomib prevents proliferation and migration of pulmonary arterial smooth muscle cells"],"prefix":"10.1002","volume":"40","author":[{"given":"Yi\u2010Ching","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-2209","authenticated-orcid":false,"given":"Yu\u2010Hsin","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hsin","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Medical Research, E\u2010Da Hospital I\u2010Shou University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Yen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chi\u2010Mei Medical Center  Tainan Taiwan"},{"name":"School of Medicine, College of Medicine National Sun Yat\u2010sen University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Childhood Education and Nursery Chia Nan University of Pharmacy and Science  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang\u2010En","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siao\u2010Ping","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jwu\u2010Lai","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Medical Research Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Graduate Institute of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Marine Biotechnology and Resources National 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