基于生物信息学分析2型糖尿病对骨骼肌微环境影响的分子机制

The molecular mechanism of influence of the type 2 diabetes mellitus on skeletal muscle microenvironment based on bioinformatics analysis

2型糖尿病T2DM是糖尿病的主要类型,该疾病影响血糖代谢从而导致肌肉细胞受损.然而,目前关于肌肉细胞受损导致肌肉组织微环境改变进而导致T2DM发病的机制仍不清楚.本研究使用美国国立生物技术信息中心基因表达数据库的基因芯片数据(GSE12643和GSE29221),选取44个肌肉样本的基因组数据进行差异基因分析和单样本基因富集(ssGSEA)分析.结果显示,T2DM组和健康对照组骨骼肌的40个差异基因分析中,发现主要和肌肉损伤疾病相关,且与T2DM酮症酸中毒、胰腺相关的慢性疾病直接相关(P<0.01).通过相关性分析发现,3个基因(ADH1B,GPX3,RARRES2)与骨骼肌微环境显著相关(R>0.6,P<0.05).该研究结果有助于加深T2DM与骨骼肌相关疾病发病分子机制的理解.

Type 2 diabetes mellitus(T2DM)is a major chronic metabolic disease that affects blood glucose metabolism and thus leads to muscle cell damage.However,no definite conclusion is reached about the molecular mechanism behind T2DM resulting from the change of the muscle microenvironment due to muscle cell damage.This study employed the microarray data(GSE12643 and GSE29221)that included 44 samples in the gene expression omnibus(GEO)database from the national center for biotechnology information(NCBI)to analyze the gene expression data of muscle tissue of T2DM as well as the differential genes and single sample gene set enrichment analysis(ssGSEA)by R software.The results showed that among the 40 differentially expressed genes in T2DM through GEO database,the up regulation genes are directly related to muscle injury diseases,and down-regulation genes are directly related to diabetic ketoacidosis and pancreatic related chronic diseases(P<0.01).Using ssGSEA,it is concluded that chondrocytes and hepatocytes are highly enriched cells in T2DM.Through correlation analysis,it is found that ADH1B,GPX3 and RARRES2 are significantly correlated with skeletal muscle microenvironment.The current study will help to deepen the understanding of the molecular mechanism behind T2DM consequence upon skeletal muscle-related diseases.