Ulinastatin inhibits hypoxia-induced phenotype modulation of pulmonary artery smooth muscle cells by up-regulating PPAR-γ expression.
- Author:
Kun TANG
1
;
Chang LIU
;
Lin CHEN
;
Jing GAO
;
Chao ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Actins; metabolism; Animals; Calcium-Binding Proteins; metabolism; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Glycoproteins; pharmacology; Microfilament Proteins; metabolism; Myocytes, Smooth Muscle; cytology; drug effects; PPAR gamma; metabolism; Phenotype; Pulmonary Artery; cytology; Rats; Rats, Sprague-Dawley; Up-Regulation
- From: Journal of Southern Medical University 2016;36(10):1322-1327
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo evaluate the effect of ulinastatin on hypoxia-induced phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) and explore the underlying mechanism.
METHODSCultured PASMCs from SD rats were exposed to normoxic condition, normoxia with ulinastatin treatment, hypoxia, or hypoxia with ulinastatin treatment. After 24 h of exposures, the cells were examined for SM-α-actin and caplonin expressions with immunofluorescence assay and for cell migration with CCK-8 andH-TdR assays. Western blotting was used for detecting the expressions of PPAR-γ in the cells, and PPAR-γ-responsive firefly luciferase reporter was employed for measuring the transcriptional activity of PPAR-γ. The PPAR-γ inhibitor GW9662 was used to explore the mechanism of the inhibitory effect of ulinastatin on hypoxia induced-phenotype modulation of PASMCs by measuring the changes in cell proliferation and migration.
RESULTSUlinastatin obviously enhanced the expressions of SM-α-actin and calponin (P<0.05), inhibited the proliferation and migration (P<0.05), and up-regulated the expression of PPAR-γ in PASMCs exposed to hypoxia (P<0.05). Pretreatment of the cells with GW9662 abolished the effect of ulinastatin on hypoxia-induced phenotype modulation of PASMCs and enhanced the cell proliferation and migration (P<0.05).
CONCLUSIONUlinastatin inhibits hypoxia-induced phenotype modulation of PASMCs from rats possibly by up-regulating the expression of PPAR-γ.
