title: BMP4 protects rat pulmonary arterial smooth muscle cells from apoptosis by PI3K/AKT/Smad1/5/8 signaling.
abstract: Bone morphogenetic protein-4 (BMP4), a member of the transforming growth factor β (TGF-β) family of growth factors, is activated and increased under hypoxic conditions, which plays an important role in the progression of pulmonary arterial hypertension (PAH). Previous studies have shown that BMP4 is involved in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. However, the precise mechanisms involved in the regulation of pulmonary artery smooth muscle cells (PASMCs) in PAH are still incompletely understood. It has been reported that AKT is a critical regulator of cell survival and vascular remodeling. Therefore, there may be crosstalk between BMP4 anti-apoptotic processes and PI3K/AKT survival effect in rat PASMCs. To test this hypothesis, we performed confocal, cell viability measurement, mitochondrial potential, real-time polymerase chain reaction (PCR), and Western blot analysis to determine the role of BMP4 on cell survival and apoptosis. We found that hypoxia up-regulated the expression of BMP4. BMP4 promoted cell survival, reduced mitochondrial depolarization, and increased the expression of Bcl-2 and procaspase-3 in PASMCs under serum-deprived condition. These effects were reversed by PI3K/AKT inhibitors (LY294002 and wortmannin). Thus, these ﬁndings indicate that BMP4 protects PASMCs from apoptosis at least in part, mediated via the PI3K/AKT pathway.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116000, China. jianwu111@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinic Technology Center of Dalian Medical University, Dalian 116000, China. zhigyu520@163.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116000, China. dechunsu1978@163.com.
authors.forename: Dechun
authors.initials: D
authors.lastname: Su
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D055415:Bone Morphogenetic Protein 4; D053148:Caspase 3; D002867:Chromones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051896:Smad Proteins, Receptor-Regulated; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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