Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, 10050, China.
Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xicheng District, Beijing, 100050, China.
Biochem Genet. 2023 Aug;61(4):1567-1584. doi: 10.1007/s10528-023-10336-6. Epub 2023 Jan 30.
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.
肾小管间质纤维化是糖尿病肾病的一个重要病理特征，与肾功能受损有关。然而，糖尿病肾病中纤维化发生的机制尚不清楚。从糖尿病患者和单侧输尿管梗阻小鼠的肾组织转录组图谱中鉴定差异表达基因，并进行交集，以获得可能参与糖尿病纤维化的基因。进行了生物功能分析和蛋白质-蛋白质相互作用网络分析。进行了枢纽基因的 ROC 曲线和 Pearson 相关性分析，并估计肾小球滤过率。最后，使用实时 PCR 测量枢纽基因的 RNA 水平。共鉴定出 283 个可能参与糖尿病肾病纤维化的基因。TYROBP、CTSS、LCP2、LUM 和 TLR7 被鉴定为异常表达的枢纽基因。免疫细胞浸润分析表明，糖尿病肾病组中细胞毒性淋巴细胞、B 细胞谱系细胞、单核细胞谱系细胞、髓样树突状细胞、中性粒细胞和成纤维细胞数量增加。TYROBP、CTSS、LCP2、LUM 和 TLR7 的 ROC 曲线下面积分别为 0.9167、0.9583、0.9917、0.93333 和 0.9583（P<0.001），与估计肾小球滤过率的相关系数分别为-0.8332、-0.752、-0.7875、-0.7567 和-0.7136（P<0.001）。高糖处理的人肾小管上皮细胞中 TYROBP、CTSS、LUM 和 TLR7 的 RNA 水平上调（P<0.005）。本研究鉴定出 TYROBP、CTSS、LCP2、LUM 和 TLR7 可能参与糖尿病肾病纤维化。此外，TYROBP、CTSS、LUM 和 TLR7 可能与肾小管上皮细胞的上皮-间充质转化有关。
