RRC ID 45028
著者 Liu S, Xu R, Gerin I, Cawthorn WP, Macdougald OA, Chen XW, Saltiel AR, Koenig RJ, Xu B.
タイトル SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and downstream signaling.
ジャーナル PLoS One
Abstract The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did or did not overexpress SRA into adipocytes using combinations of methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA overexpression promotes full adipogenesis in part by stimulation of insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells. Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor (IR) mRNA and protein levels, which led to decreased autophosphorylation of IRβ and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. This likely reflects a stimulatory role of SRA on IR transcription, as transfection studies showed that SRA increased expression of an IR promoter-luciferase reporter construct.
巻・号 9(4)
ページ e95416
公開日 2014-1-1
DOI 10.1371/journal.pone.0095416
PII PONE-D-13-26117
PMID 24743795
PMC PMC3990642
MeSH 3T3 Cells Adipogenesis / genetics Adipogenesis / physiology* Animals Cell Line Humans Immunoblotting JNK Mitogen-Activated Protein Kinases / metabolism* Mice Phosphorylation RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism* Receptor, Insulin / genetics Receptor, Insulin / metabolism* Signal Transduction / physiology p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism*
IF 2.74
引用数 22
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 ST2(RCB0224)