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Secretory clusterin is upregulated in rats with pulmonary arterial hypertension induced by systemic-to-pulmonary shunts and exerts important roles in pulmonary artery smooth muscle cells.
MedLine Citation:
PMID:  25069740     Owner:  NLM     Status:  Publisher    
AIM: Phenotype modification of pulmonary artery smooth muscle cells (PASMCs) (excessive proliferation, migration and impaired apoptosis) plays central roles in pulmonary vascular remodeling 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 remodeling.
METHODS: 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 were collected for enzyme linked immunosorbent assay. Cell culture experiments were performed using cultured human PASMCs (HPASMCs).
RESULTS: 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 signaling pathways.
CONCLUSION: 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 remodeling. This article is protected by copyright. All rights reserved.
Xiaoyan Liu; Liukun Meng; Jun Li; Jian Meng; Xiao Teng; Haiyong Gu; Shengshou Hu; Yingjie Wei
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-29
Journal Detail:
Title:  Acta physiologica (Oxford, England)     Volume:  -     ISSN:  1748-1716     ISO Abbreviation:  Acta Physiol (Oxf)     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262545     Medline TA:  Acta Physiol (Oxf)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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