Whole Transcriptomic Identification and Characterization of Potential ceRNA Regulatory Networks in Perirenal Adipose Tissue of Type-2-Diabetic Mellitus SD Rats With Diabetic Nephropathy.

Abstract

This study induced diabetic nephropathy (DN) in rats, analyzing perirenal adipose tissue (PRAT) via whole transcriptome sequencing to identify key mRNAs in DN pathogenesis. Type-2 diabetes was induced in SD rats, evaluating metabolic and renal indicators. Whole transcriptome sequencing identified differentially expressed RNAs in PRAT. CeRNA networks, PPI networks, and ingenuity pathway analysis (IPA) revealed key mRNAs linked to physiological indicators in DN. This study explores correlations between mRNAs and health parameters, shedding light on the complex interplay in type-2-diabetes mellitus (T2DM)-induced nephropathy. SD rats with type-2 diabetes exhibited insulin resistance, elevated blood glucose, disrupted lipid metabolism, and renal dysfunction. PRAT weight was higher in T2DM rats, and immunohistochemistry revealed distinct renal injury. Transcriptome sequencing identified 476 DE-mRNAs, 79 DE-miRNAs, 200 DE-lncRNAs, and 10 DE-circRNAs. The lncRNA-miRNA-mRNA network comprised 159 lncRNAs, 62 miRNAs, and 138 mRNAs, whereas the circRNA-miRNA-mRNA network included 76 mRNAs, 27 miRNAs, and 10 circRNAs. Key mRNAs (Lpl, Elovl6, Dgat2, Acaca, and Acly) were associated with 10 classical pathways according to IPA. Notably, all key mRNAs showed a negative correlation with blood urea nitrogen (BUN), serum creatinine, proteinuria, LDL-C, triglycerides (TG), and total cholesterol (TC), and a positive correlation with urine creatinine and HDL-C. Our study successfully established a T2DM model in SD rats and identified five key mRNAs, elucidating the role of PRAT in DN. These findings lay a scientific foundation for future investigations into DN.