BACKGROUND Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 (PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated. METHODS Monocrotaline (MCT 60 mg/kg) was used to build a PAH model in SD rats. Right ventricular systolic pressure (RVSP) and right ventricle (RV) hypertrophy were measured. Morphology of pulmonary vessels was observed by Hematoxylin-Eosin (HE) staining. Expression of PHB1 in pulmonary arteries and PASMCs was determinated by immunoblot and immunofluorescence. Cell proliferation was detected by CCK8 and EDU when PASMCs were stimulated by PDGF-BB (20 ng/mL). Furthermore, siRNA for PHB1 and Akt inhibitor were conducted to investigate the mechanism behind the role of PHB1 and AKT signaling pathway in PASMCs proliferation and apoptosis. RESULTS The protein expression of PHB1 in PAH rats lung tissue was significantly up-regulated accompanied by elevated RVSP and enhanced RV hypertrophy. Immunohistochemistry showed that PHB1 was mainly localized in the pulmonary vascular smooth muscle layer. PDGF-BB significantly up-regulated the expression of PHB1 in rat primary PASMCs in a time- and dose-dependent manner. After PHB1 knock down, PASMCs proliferation was significantly suppressed while apoptosis was significantly recovered. Meanwhile the level of proliferating cell nuclear antigen (PCNA) and P-Akt were significantly down-regulated. Perifosine (Akt inhibitor) also significantly inhibit proliferation of PASMCs. CONCLUSION PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation.

中文翻译：

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抑制素1对一丁crocroline诱导的PAH大鼠肺动脉平滑肌细胞增殖和凋亡的调节作用。

背景技术肺动脉高压（PAH）是一种严重的肺血管疾病，其特征在于肺动脉平滑肌细胞（PASMC）的增殖和凋亡不平衡。抑制素1（PHB1）以其显着的抗增殖活性而闻名。但是，尚未阐明PHB1在PASMC和PAH中的作用。方法采用单肾上腺素（MCT 60 mg / kg）建立SD大鼠PAH模型。测量右心室收缩压（RVSP）和右心室（RV）肥大。通过苏木精-曙红（HE）染色观察肺血管的形态。通过免疫印迹和免疫荧光测定肺动脉和PASMC中PHB1的表达。当PDGF-BB（20 ng / mL）刺激PASMCs时，CCK8和EDU检测到细胞增殖。此外，为了研究PHB1和AKT信号通路在PASMCs增殖和凋亡中的作用背后的机制，进行了PHB1和Akt抑制剂的siRNA研究。结果PAH大鼠肺组织PHB1蛋白表达明显上调，伴有RVSP升高和RV肥大。免疫组织化学显示，PHB1主要位于肺血管平滑肌层。PDGF-BB以时间和剂量依赖性方式显着上调大鼠原发性PASMC中PHB1的表达。在PHB1敲低后，PASMCs的增殖被显着抑制，而凋亡则被显着恢复。同时，增殖细胞核抗原（PCNA）和P-Akt的水平明显下调。Perifosine（Akt抑制剂）还可以显着抑制PASMC的增殖。