Identification of fibrosis-associated lncRNAs in diabetic cardiomyopathy patients.

Abstract

Introduction: Our study endeavours to ascertain the plasma-derived long noncoding ribonucleic acids (lncRNA) and messenger RNA (mRNA) expression profiles through gene microarray analysis, aiming to elucidate their potential biological roles in the development and progression of diabetic cardiomyopathy (DCM), particularly with respect to myocardial fibrosis.

Material and methods: We conducted gene chip experiments to discern differences in lncRNA and mRNA expression profiles between diabetic cardiomyopathy and type 2 diabetes mellitus (T2DM). Differentially expressed mRNAs were subjected to functional enrichment analysis, thereby enabling the identification of key genes. Subsequently, we established an interaction network connecting lncRNAs with mRNAs. To validate myocardial fibrosis-related mRNAs, we further developed a rat model of diabetic cardiomyopathy.

Results: We identified 688 differentially expressed lncRNAs and 341 differentially expressed mRNAs, which were primarily enriched in creatine metabolism, small guanosine triphosphate hydrolase (GTPase)-mediated signal transduction, and fatty acid degradation processes. Our analyses revealed 8 core genes (SMD11, DRG1, RPS26, EIF2S1, UBE3A, CEBPZ, NUP153, and EMD) associated with diabetic cardiomyopathy. An investigation into the lncRNA-mRNA coexpression network underscored 4 lncRNAs (lnc-NEK10-3, lnc-KDM4A-2, lnc-PCYOX1-3, and lnc-CDCP2-1) as significantly linked to differentially expressed fibrosis-associated mRNAs. The expression levels of transmembrane protein 173 (TMEM173) and toll-like receptor 7 (TLR7) were found to be significantly higher in DCM compared to normal controls, whereas cathepsin L1 (CTSL) and forkhead box O3 (FOXO3) displayed significantly lower expression levels relative to those of normal controls.

Conclusions: Our study disclosed a subset of lncRNAs and mRNAs that are implicated in diabetic cardiomyopathy and myocardial fibrosis, thereby presenting themselves as promising biomarkers and therapeutic targets for the management of both diabetic cardiomyopathy and myocardial fibrosis.