Changing Expression Profiles of lncRNAs During Ischemia-Reperfusion-Induced Renal Fibrosis

Abstract

The pathological physiology of end-stage renal disease is characterized by renal fibrosis, for which suitable therapeutics have not yet been developed. Early tubular damage in ischemia-reperfusion (IR) injury induced acute kidney injury (AKI) is highly relevant to later fibrosis, but the mechanism remains unclear. Moreover, more and more evidence has proven that long non-coding ribonucleic acids (lncRNA) regulate gene expression associated with renal fibrosis. Therefore, we analyzed lncRNA profiles in the kidneys of mice using RNA sequencing during the pathogenesis of IR-induced renal fibrosis. Our results showed that expression levels of 43 lncRNAs and 141 lncRNAs were respectively significantly changed 7 days and 2 weeks after IR treatment. We predicted the functions of the differentially expressed (DE) lncRNAs and target genes with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Interaction networks of lncRNAs, microRNAs (miRNAs) and mRNA were constructed based on the correlation analysis of the DE genes. Based on these informations, we further verified lncRNA (Gm12840) play competing endogenous RNA (ceRNA) mechanism with miR-677-5p to meidiate TGF-β1 induced fibroblast activation via Wnt-induced secreted protein-1 (WISP1)/ protein kinase B (Akt) signaling pathway. Our findings identify that lncRNAs are involved in IR-induced late fibrosis of kidney and may represent a systematic perspective on the important function of IR-induced renal fibrosis as well as new therapeutic targets. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (81860130), Natural Science Foundation of Guangdong province (2016A030313376), Guangdong Province Science and Technology Planning Project (2017B020247035, 2014A020212612). Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: All experiments using animals were approved by the Institutional Animal Care and Use Committee of the First People hospital of Foshan and breed as approved by the Institutional Animal Care protocol.