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Berberine attenuates hypoxia‐induced pulmonary arterial hypertension via bone morphogenetic protein and transforming growth factor‐β signaling
Author(s) -
Chen Mingxing,
Shen Hui,
Zhu Linlin,
Yang Hongfeng,
Ye Peng,
Liu Pengfei,
Gu Yue,
Chen Shaoliang
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28370
Subject(s) - hypoxia (environmental) , berberine , bone morphogenetic protein , pulmonary hypertension , transforming growth factor , bmpr2 , signal transduction , medicine , pharmacology , microbiology and biotechnology , endocrinology , chemistry , cardiology , biology , biochemistry , organic chemistry , oxygen , gene
Hypoxia‐induced excessive pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in the pathology of pulmonary arterial hypertension (PAH). Berberine (BBR) is reported as an effective antiproliferative properties applied in clinical. However, the effect of BBR on PAH remains unclear. In the present study, we elucidated the protective effects of BBR against abnormal PASMC proliferation and vascular remodeling in chronic hypoxia‐induced hearts. Furthermore, the potential mechanisms of BBR were investigated. For this purpose, C57/BL6 mice were exposed to chronic hypoxia for 4 weeks to mimic severe PAH. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased the right ventricular systolic pressure (RVSP), the right ventricle/left ventricle plus septum RV/(LV + S) weight ratio, and the median width of pulmonary arterioles. BBR attenuated the elevations in RVSP and RV/(LV + S) and mitigated pulmonary vascular structure remodeling. BBR also suppressed the hypoxia‐induced increases in the expression of proliferating cell nuclear antigen (PCNA) and of α‐smooth muscle actin. Furthermore, administration of BBR significantly increased the expression of bone morphogenetic protein type II receptor (BMPR‐II) and its downstream molecules P‐smad1/5 and decreased the expression of transforming growth factor‐β (TGF‐β) and its downstream molecules P‐smad2/3. Moreover, peroxisome proliferator‐activated receptor γ expression was significantly decreased in the hypoxia group, and this decrease was reversed by BBR treatment. Our study demonstrated that the protective effect of BBR against hypoxia‐induced PAH in a mouse model may be achieved through altered BMPR‐II and TGF‐β signaling.