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An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis.

ABSTRACT: Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identified 12,979 novel lncRNAs in mouse. The expression profiles of both mRNAs and lncRNAs were differed significantly between LN and control mice. In particular, there were more upregulated lncRNAs and mRNAs than downregulated ones in the kidney tissues of LN mice. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response-associated pathways. KEGG analysis showed that both downregulated and upregulated genes were enriched in a number of pathways, including the SLE pathway, and approximately half of these SLE-associated genes encoded inflammatory factors. Moreover, we observed that 2,181 DElncRNAs may have targeted and regulated the expression of 778 mRNAs in LN kidney tissues. The results of this study showed that 11 DElncRNAs targeted and were co-expressed with six immune and SLE-associated genes. qPCR analysis confirmed that lncRNA Gm20513 positively regulated the expression of the SLE-associated gene H2-Aa. In conclusion, the results of our study demonstrates that lncRNAs influence the progression of LN and provide some cues for further study of lncRNAs in LN. These results regarding the lncRNA-mRNAregulatory network may have important value in LN diagnosis and therapy.

SUBMITTER: Wang J

PROVIDER: S-EPMC7894116 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis.

Wang Juan J Wu Xiongfei X Tu Yafang Y Dang Jianzhong J Cai Zhitao Z Liao Wenjing W Quan Weili W Wei Yaxun Y

PeerJ 20210216

Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identifie ...[more]

PMID: 33628632

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Project description:IntroductionLupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis.MethodsTo characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein-protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology/Renal Pathology Society (ISN/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software.ResultsA total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell-cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV.ConclusionsThe DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.

Dataset Information

An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis.

Publications

An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis.

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