{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:16:38Z","timestamp":1789917398676,"version":"4.0.1"},"reference-count":35,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL088261"],"award-info":[{"award-number":["HL088261"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL115078"],"award-info":[{"award-number":["HL115078"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005640","name":"Flight Attendant Medical Research Institute (FAMRI)","doi-asserted-by":"publisher","award":["140083"],"award-info":[{"award-number":["140083"]}],"id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs (VA)","doi-asserted-by":"publisher","award":["BX002035"],"award-info":[{"award-number":["BX002035"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association (AHA)","doi-asserted-by":"publisher","award":["16POST27730023"],"award-info":[{"award-number":["16POST27730023"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:p> In the present study, we investigated the effect of bone morphogenetic protein 4 (BMP4) on PDGF-induced cell proliferation and collagen synthesis in pulmonary artery smooth muscle cells (PASMCs). Normal human PASMCs were incubated with and without PDGF-BB in the absence and presence of BMP4 for 0.5 to 24 h. The protein levels of collagen-I, p-Smad2\/3, p-Smad1\/5, and intracellular active TGF-\u03b21, calpain activity, and cell proliferation were then measured. The results showed that BMP4 induced an increase in p-Smad1\/5 but had no effect on the protein levels of collagen-I, p-Smad2\/3, and intracellular active TGF-\u03b21 and calpain activity in control PASMCs. Nevertheless, BMP4 attenuated increases in cell proliferation and protein levels of collagen-I, p-Smad2\/3, and intracellular active TGF-\u03b21 and calpain activity in PASMCs exposed to PDGF-BB. Moreover, BMP4 increased PKA activity and inhibition of PKA prevented the inhibitory effects of BMP4 on PDGF-BB-induced calpain activation in normal PASMCs. The PKA activator forskolin recapitulated the suppressive effect of BMP4 on PDGF-induced calpain activation. Furthermore, BMP4 prevented a PDGF-induced decrease in calpain-2 phosphorylation at serine-369 in normal PASMCs. Finally, BMP4 did not attenuate PDGF-induced increases in cell proliferation, collagen-I protein levels, and calpain activation and did not induce PKA activation and did not prevent a PDGF-induced decrease in calpain-2 phosphorylation at serine-369 in PASMCs from idiopathic pulmonary arterial hypertension (PAH) patients. These data demonstrate that BMP4 inhibits PDGF-induced cell proliferation and collagen synthesis via PKA-mediated inhibition of calpain-2 in normal PASMCs. The inhibitory effects of BMP4 on PDGF-induced cell proliferation, collagen synthesis, and calpain-2 activation are impaired in PASMCs from PAH patients, which may contribute to pulmonary vascular remodeling in PAH. <\/jats:p>","DOI":"10.1152\/ajplung.00260.2016","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T20:50:19Z","timestamp":1487969419000},"page":"L638-L648","source":"Crossref","is-referenced-by-count":24,"title":["BMP4 inhibits PDGF-induced proliferation and collagen synthesis via PKA-mediated inhibition of calpain-2 in pulmonary artery smooth muscle cells"],"prefix":"10.1152","volume":"312","author":[{"given":"Pengcheng","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;"},{"name":"Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;"},{"name":"Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia;"},{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;"},{"name":"Research Service, Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; 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