Abstract
Tubulointerstitial fibrosis is an important pathological feature of diabetic nephropathy that is associated with impaired renal function. However, the mechanism by which fibrosis occurs in diabetic nephropathy is unclear. Differentially expressed genes were identified from transcriptome profiles of renal tissue from diabetic patients and unilateral ureteral obstruction mice and intersected to obtain genes that may be involved in diabetic fibrosis. Biological function analysis and protein–protein interaction network analysis were performed. ROC curve and Pearson correlation analysis between hub genes were performed and glomerular filtration rate estimated. Finally, the RNA levels of hub genes were measured using real-time PCR. A total of 283 genes were identified as potentially involved in diabetic nephropathy fibrosis. TYROBP, CTSS, LCP2, LUM and TLR7 were identified as aberrantly expressed hub genes. Immune cell infiltration analysis demonstrated higher numbers of cytotoxic lymphocytes, B lineage cells, monocyte lineage cells, myeloid dendritic cells, neutrophils, and fibroblasts in the diabetic nephropathy group. The areas under ROC curves for TYROBP, CTSS, LCP2, LUM and TLR7 were 0.9167, 0.9583, 0.9917, 0.93333, and 0.9583, respectively (P < 0.001), and their correlation coefficients with estimated glomerular filtration rate were − 0.8332, − 0.752, − 0.7875, − 0.7567, and − 0.7136, respectively (P < 0.001). The RNA levels of TYROBP, CTSS, LUM and TLR7 were upregulated in high-glucose-treated human renal tubular epithelial cells (P < 0.005). Our study identified TYROBP, CTSS, LCP2, LUM and TLR7 as potentially involved in diabetic nephropathy fibrosis. Furthermore, TYROBP, CTSS, LUM and TLR7 may be associated with epithelial–mesenchymal transition of tubular epithelial cells.
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All data generated or analysed during this study are included in this published article [and its supplementary information files].
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Acknowledgements
We thank Wei Chen, PhD, from Beijing Friendship Hospital for his assistance with bioinformatics methodologies. We also thank Jeremy Allen, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing a draft of this manuscript.
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This study was supported by the Wu Jieping Medical Foundation (code 32067502021–11-26) and the Beijing Municipal Administration of Hospitals Incubating Program (code PX2022003).
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The roles and responsibilities of authors were: YB: design, analysis, and interpretation of data, drafting and revising the article. LM: analysis and interpretation of data. DD and DT: providing intellectual content of critical importance to the work described. WL and ZD: providing intellectual content of critical importance to the work described and final approval of the version to be published.
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Bai, Y., Ma, L., Deng, D. et al. Title: Bioinformatic Identification of Genes Involved in Diabetic Nephropathy Fibrosis and their Clinical Relevance. Biochem Genet 61, 1567–1584 (2023). https://doi.org/10.1007/s10528-023-10336-6
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DOI: https://doi.org/10.1007/s10528-023-10336-6