SOX4 As Gestational Diabetes Molecular Diagnostic Marker Of Appraisal And Its Pathogentic Mechanism

PART I THE RESEARCH OF THE EFFECTIVENESS OF SOX4 AS MOLECULAR DIAGNOSTIC MARKER FOR GDMBackgroundGenome-wide association studies(GWAS)indicated that overexpression of SOX4 mediated type-2 diabetes linked to an intronic SNP in CDKAL1,suggesting the potential of SOX4 as molecular marker for diagnosis of Gestational Diabetes Mellitus(GDM).In addition,SOX4 is a key transcription factor during embryo development,indicating its important role in blood sugar regulation during gestation.We thus deduce that there should be aberrant elevated expression of SOX4 in women with gestational diabetes mellitus ?ObjectiveTo investigate if or not there is different in circulating RNA,serum protein,cellular RNA and protein of SOX4 between normal pregnancy control and GDM.sufferers?MethodsCirculating RNA extraction kit coupled with quantitative real-time polymerase chain reaction were used for SOX4 circulating RNA and cellular RNA detection.Western-blot was adopted for SOX4 protein detection.ResultsSignificant elevation in circulating RNA,serum protein,cellular RNA and protein of SOX4 was observed in GDM sufferersConclusionsThe levels of circulating RNA,serum protein,cellular RNA and protein of SOX4 were significantly increased in GDM sufferers.However,as the low basal expression level,the protein in both serum and blood cell can not be diagnostic marker.Bigger sample sized should be involved to evaluate the efficiency of SOX4 circulating RNA as diagnostic marker for GDM.PART II THE RESEARCH OF MECHANISMS UNDERLYING SOX4 INDUCED INSULIN RESISTANCE.Background:Type 2 diabetes comprises 90% of people with diabetes around the world.Mechanisms underlying Type 2 diabetes is complex,including genetics and environment factors.GDM shares features with Type 2diabetes,indicating similar regulatory mechanisms occurs in GDM patients.Understanding the molecular mechanisms underlying GDM is helpful for its precision therapy.Recently,Genome-wide association studies(GWAS)indicated that overexpression of SOX4 mediated type 2 diabetes linked to an intronic SNP in CDKAL1,suggesting the potential of SOX4 as molecular marker for diagnosis of Gestational Diabetes Mellitus(GDM).In addition,SOX4 is a key transcription factor during embryo development,indicating its important role in blood sugar regulation during gestation.We thus deduce aberrant elevated expression of SOX4 improves insulin resistant of the cells in Gestational Diabetes Mellitus sufferers.However,the mechanisms of action for this is remained elusive.ObjectiveThe objective of this study is to reveal the mechanisms underlyingSOX4 induced insulin resistance.Methods3T3-L1 cell line was chosen as cell model.Gene expression and knockdown was performed by lentivirus system.Western-blot and q RT-PCR were used to detect the gene expression.Reporter gene assay as used to determine the activity of promoters.Elisa was used to examine the concentration of TNF-? and glucose uptake.ResultsSOX4 forms a feedback loop with TNF-? and inhibits PI3K/AKT signaling pathway and thus inhibits membrane translocation of Glut4 and glucose uptake.ConclusionsSOX4 inhibits Glut4 membrane translocation and glucose uptake via TNF-? and TNF-? induced PI3K/AKT signaling pathway inhibition.