Drug-induced nephrotoxicity(DIN)is a common adverse effect during drug development phase.However,conventional serum biomarkers of renal injury,such as blood urea nitrogen and serum creatinine,lack sensitivity and specificity.It is crucial to discover superior novel biomarkers of DIN.In this study,a DIN model was constructed by intramuscular injection of 80 mg/kg of gentamicin sulphate(GEN)in SD rats,and plasma exosomal lncRNA and mRNA expression profiles were evaluated by RNA sequencing.Differentially expressed(DE)lncRNAs were identified and validated through real-time reverse transcription quntitative PCR(RT-qPCR)assays.The functional roles of DE mRNAs were elucidated using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Additionally,coding/non-coding co-expression and competing endogenous RNAs(ceRNAs)network to unveil potential relationships in DIN were established.The results showed that 500 differentially expressed(DE)lncRNAs and 1 027 DE mRNAs were identified,the latter primarily associated with signal transduction and the immune system.The established ceRNAs co-expression and regulation networks comprised 32 upregulated lncRNAs,151 downregulated miRNAs,and 42 upregulated mRNAs.Through RT-qPCR,NONRATT021116.2 and NONRATT004088.2 were found notably upregulated in rat blood.Then,NONRATT021116.2/miRNA/mRNA and NONRATT004088.2/miRNA/mRNA ceRNA networks were constructed.Notably,let-7b-5p exhibited a high association with NONRATT021116.2,suggesting potential involvement in modulating inflammatory responses.This study reveals DE lncRNAs and mRNAs in DIN rats using sequencing techniques.Further exploration of these lncRNAs promises insights into the genetic mechanisms underlying DIN and may lead to the identification of diagnostic markers and therapeutic targets.
维普
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