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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
Author(s) -
Liu X.,
Meng L.,
Li J.,
Meng J.,
Teng X.,
Gu H.,
Hu S.,
Wei Y.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12352
Subject(s) - clusterin , downregulation and upregulation , pulmonary artery , vascular remodelling in the embryo , western blot , pulmonary hypertension , lung , apoptosis , medicine , cancer research , pathology , chemistry , cardiology , biochemistry , gene
Aim Phenotype modification of pulmonary artery smooth muscle cells ( PASMC s) (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 PASMC s are still not completely elucidated. This study attempted to investigate the expression pattern of secretory clusterin (s CLU ), a prosurvival protein, in systemic‐to‐pulmonary shunt‐induced PAH rats and the potential roles of s CLU in pulmonary vascular remodelling. 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 was collected for enzyme‐linked immunosorbent assay. Cell culture experiments were performed using cultured human PASMC s ( HPASMC s). 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 s CLU expression and secretion increased with the phenotype modification of HPASMC s; furthermore, s CLU promoted HPASMC s proliferation, migration and apoptosis resistance, at least in part, via E rk1/2 and A kt signalling pathways. Conclusion These results demonstrate that s CLU is functionally an important phenotype modulator of PASMC s, and its upregulation in lung tissues may exert a deteriorative role in pulmonary vascular remodelling.