MG-treated vs non-treated ST2 cells Mouse 32K
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Sohei Kitazawa
PROVIDER: E-GEOD-52475 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In diabetics, methylglyoxal (MG), a glucose-derived metabolite, plays a noxious role by inducing oxidative stress, which causes and exacerbates a series of complications. With the use of microarray analysis, we comprehensively screened the gene expression profiles of ST2 cells, derived from a multipotent bone marrow stromal cell line, in the presence or absence of oxidative stress induced by100 μM methylglyoxal (MG) treatment to charactrize genes related to diabetic complications.
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Project description:PPARM-NM-3 is a master transcriptional regulator of adipogenesis. Hence, the identification of PPARM-NM-3 coactivators should help reveal mechanisms controlling gene expression in adipose tissue development and physiology. We show that the non-coding RNA Steroid receptor RNA Activator, SRA, associates with PPARM-NM-3 and coactivates PPARM-NM-3-dependent reporter gene expression. Overexpression of SRA in ST2 adipocyte precursor cells promotes their differentiation into adipocytes. Conversely, knockdown of endogenous SRA inhibits 3T3-L1 preadipocyte differentiation. Microarray analysis reveals hundreds of SRA-responsive genes in adipocytes, including genes in cell cycle, insulin and TNFM-NM-1 signaling pathways. Some functions of SRA may involve mechanisms other than coactivation of PPARM-NM-3. SRA increases insulin-stimulated glucose uptake in adipocytes. SRA promotes S-phase entry during mitotic clonal expansion, decreases expression of cyclin-dependent kinase inhibiters p21Cip1 and p27Kip1, and increases phosphorylation of Cdk1/Cdc2. SRA also inhibits the TNFM-NM-1-induced phosphorylation of c-Jun NH2-terminal kinase. In conclusion, SRA enhances adipogenesis and adipocyte function through multiple pathways. Total RNA was isolated from fully differentiated (MDIT day 4) SRA overexpressing (pMSCV-SRA) and control (pMSCV empty vector) ST2 adipocytes, or fully differentiated (MDIT day 8) shSRA knockdown (pSuperior-shSRA) or shControl (pSuperior-shcontrol) 3T3-L1 adipocytes. Genome wide gene expression analysis was performed using Affymetrix mouse genome 430 2.0 arrays. Triplicate samples were analyzed.
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