小鼠肾脏衰老过程中长链非编码 RNA 的差异表达

Objective To analyze the differentally expressed long non-coding RNA (lncRNA) among mice of different ages and explore the mechanism of kidney aging. Methods Male C57BL/6 mice aged 3 - month - old (n=5), 12 - month - old (n=5) and 24 - month - old (n=5) (each weighting about 25 g) were randomly selected. PAS staining, Masson staining and senescence associated β - galactosidase (SA - β - gal) staining were used to detect the pathology and cell senescence of mice kidney. High throughput sequencing was performed to detect the differentially expressed lncRNA and their fragments per kilobase million. Real - time quantitative PCR was used to verify the differentially expressed lncRNA. Competitive endogenous RNA (ceRNA) network, which consisted of lncRNA, miRNA and mRNA was built. GO and KEGG enrichment analysis method were used to predict the biological function of differentially expressed lncRNA. Results PAS staining and Masson staining showed the development of kidney fibrosis, and SA - β - gal staining positive region was increased significantly as age increased. There were 938 known lncRNA and 542 novel lncRNA differentially expressed among different ages' mouse kidney. Compared with 3 - month - old mice, 33 lncRNA were up - regulated and 43 lncRNA were down - regulated in 12 - month - old mice. Compared with 3 - month - old mice, 130 lncRNA were up - regulated and 91 lncRNA were down - regulated in 24 - month - old mice. Compared with 12 - month - old mice, 36 lncRNA were up - regulated and 22 lncRNA were down - regulated in 24 - month - old mice. The results of qRT - PCR about verified 10 lncRNAs with larger differential expression multiples and higer expression levels were consistent with the sequencing data. GO enrichment analysis showed that the target genes of lncRNA differentially expressed in the three groups were mostly located in the nucleus and cytoplasm, and might play a role by binding to proteins or participate in various protein phosphorylation, cell cycle, transcription, transcription regulation and other processes. KEGG enrichment analysis showed that the target genes of lncRNA differentially expressed in the three group were significantly enriched in Rap1 signaling pathway, FOXO signaling pathway and MAPK signaling pathway, which were closely related to kidney aging. Conclusion There are significant differences in expression of lncRNA among the kidney of different ages mice, which are involved in the occurrence of renal senescence.