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) |