XCT790 inhibits rat vascular smooth muscle cells proliferation through down-regulating the expression of estrogen-related receptor alpha.
- Author:
Yun-Hong LU
;
Qun-Yi LI
;
Li CHEN
;
Xiao-Jin SHI
- Publication Type:Journal Article
- MeSH:
Animals;
Cadherins;
genetics;
metabolism;
Cell Proliferation;
drug effects;
Cells, Cultured;
Cytoskeletal Proteins;
genetics;
metabolism;
Dose-Response Relationship, Drug;
GTPase-Activating Proteins;
genetics;
metabolism;
MAP Kinase Signaling System;
Male;
Muscle, Smooth, Vascular;
cytology;
Myocytes, Smooth Muscle;
cytology;
drug effects;
metabolism;
Nitriles;
administration & dosage;
pharmacology;
Nuclear Proteins;
genetics;
metabolism;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha;
Phosphorylation;
RNA, Messenger;
metabolism;
Rats;
Rats, Sprague-Dawley;
Receptors, Estrogen;
genetics;
metabolism;
Thiazoles;
administration & dosage;
pharmacology;
Transcription Factors;
genetics;
metabolism;
Vascular Endothelial Growth Factor A;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2014;49(2):190-197
- CountryChina
- Language:Chinese
-
Abstract:
Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in several pathological processes of cardiovascular diseases. In this study, the effects of XCT790, a potent and selective inverse agonist of estrogen-related receptor alpha (ERRalpha), on rat VSMCs proliferation and related signal pathways were investigated. The proliferative activity of VSMCs was determined by CCK-8 assay. The mRNA levels of ERRalpha, PGC-1alpha, OPN and MCAD were assayed by RT-PCR. The protein levels of ERRalpha, ERK2 and p-ERK1/2 were evaluated by Western blotting. ELISA was used to assess the protein expression of VEGF. The results showed that XCT790 (5-20 micromol x L(-1)) inhibited rat VSMCs proliferation, and the expression of ERRalpha and its target genes, as well as p-ERK1/2, were also inhibited. XCT790 inhibited VSMCs proliferation in a dose-dependent manner at the dose range from 5 to 20 micromol x L(-1) and in a time-dependent manner at the dose range from 10 to 20 micromol x L(-1). These findings demonstrate that XCT790 inhibits rat VSMCs proliferation by down-regulating the gene level of ERRalpha and thus inhibiting the ERK signal pathway, suggesting that ERRalpha may be a novel potential target for therapeutic approaches to inhibit VSMCs proliferation, which plays an important role in several cardiovascular diseases.
