凝集素
下调和上调
肺动脉
胚胎血管重塑
免疫印迹
肺动脉高压
肺
细胞凋亡
医学
癌症研究
病理
化学
心脏病学
内科学
生物化学
基因
作者
X. Liu,Lingling Meng,J. Li,Jian Meng,Xiao Teng,Heng Gu,Shengshou Hu,Yingjie Wei
摘要
Phenotype modification of pulmonary artery smooth muscle cells (PASMCs) (excessive proliferation, migration and impaired apoptosis) plays central roles in pulmonary vascular remodelling of pulmonary arterial hypertension (PAH); however, the potential mechanism and contributing factors involved in the phenotype alteration in PASMCs are still not completely elucidated. This study attempted to investigate the expression pattern of secretory clusterin (sCLU), a prosurvival protein, in systemic-to-pulmonary shunt-induced PAH rats and the potential roles of sCLU in pulmonary vascular remodelling.An original rat model of systemic-to-pulmonary shunt-induced PAH was established by combined surgery as we previously reported. Lung tissues were harvested at specific time points for real-time polymerase chain reaction, Western blot and immunohistochemisty analysis; meanwhile, plasma was collected for enzyme-linked immunosorbent assay. Cell culture experiments were performed using cultured human PASMCs (HPASMCs).Expression of sCLU was significantly increased in lungs exposed to systemic-to-pulmonary shunt. Moreover, plasma sCLU levels were markedly elevated with the progression of PAH in rats and also presented a positive correlation with pulmonary hemodynamic indices. In vitro cell culture assay indicated that sCLU expression and secretion increased with the phenotype modification of HPASMCs; furthermore, sCLU promoted HPASMCs proliferation, migration and apoptosis resistance, at least in part, via Erk1/2 and Akt signalling pathways.These results demonstrate that sCLU is functionally an important phenotype modulator of PASMCs, and its upregulation in lung tissues may exert a deteriorative role in pulmonary vascular remodelling.
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