title: Schisandrin B displays a protective role against primary pulmonary hypertension by targeting transforming growth factor β1.
abstract: Pulmonary arterial smooth muscle cells (PASMCs) in the medial layer of the vessel wall are involved in vessel homeostasis, but also for pathologic vascular remodeling in diverse diseases, such as pulmonary arterial hypertension (PAH). Pulmonary vascular remodeling in PAH results in vascular disorders, but its underlying molecular mechanisms are still not to be fully disclosed. In this study, we investigated the expression and function of the transforming growth factor (TGF)-β1 in human PASMC cultured under the condition of hypoxia and elucidated the effect of schisandra chinensis and its active ingredients on proliferation, migration, and apoptosis in human PASMCs. We demonstrated that schisandrin B (Sch.B) alleviated the severity of PAH in PASMCs cultured under the condition of hypoxia. Significant upregulation of TGF-β1 was observed in hypoxia-induced human PASMCs. Interestingly, administration of Sch.B substantially attenuated TGF-β1 level in these PASMCs. In order to elucidate Sch.B function, the hypoxia-induced human PASMC was stimulated with Sch.B or cotreatment with TGF-β1 in vitro. In agreement with its TGF-β1-reducing effect, Sch B relieved human PASMCs migration and promoted the apoptosis of human PASMCs, by activation of TGF-β1 downstream signal pathways in PASMCs. In contrast, co-treatment with TGF-β1 promoted human PASMC proliferation and migration and inhibited the apoptosis of human PASMC, which can attenuate the protective role of Sch.B in human PASMC. Taken collectively, these findings suggest that the vascular relaxation evoked by Sch.B was mediated by direct effect on vascular smooth muscle cell via TGF-β1 downstream signal pathways.
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, The Third Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Key Laboratory of Cardiovascular Medicine Research, Harbin, Heilongjiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bu
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Guangnan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: chenyanjunhyd@163.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000473:pathology; D007120:Immunochemistry; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008516:Medicine, Chinese Traditional / Q000379:methods; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle; D011083:Polycyclic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000166:cytology; D032141:Schisandra / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C015499:schizandrin B
keywords: Apoptosis; proliferation; pulmonary arterial hypertension; schisandra chinensis