Ding Yingxue, Diao Zongli, Cui Hong, Yang Aijun, Liu Wenhu, Jiang Lina
Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China.
Nephrology Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China.
Transl Pediatr. 2021 Sep;10(9):2250-2268. doi: 10.21037/tp-21-83.
Proteinuria is a sensitive hallmark for progressive renal dysfunction. Transgelin (TAGLN) has been demonstrated to participate in etiology of proteinuria and dynamics of podocyte foot process; however, the mechanism of TAGLN involvement in proteinuria is unknown. The present study aimed to explore the roles of TAGLN in the development of proteinuria.
Differentially expressed genes (DEGs) were detected from microarray expression profiling datasets from Gene Expression Omnibus, and analyzed by the short time series expression miner to cluster the DEGs in proteinuria progression. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to determine the top 20 enriched pathways, and construct a gene interaction network.
In total, 2,409 DEGs for nephropathy and 10,612 DEGs for podocyte foot process and proteinuria were detected. Additionally, 76 common DEGs (25 upregulated and 41 downregulated) between nephropathy and podocyte foot process were primarily involved in innate immunity, positive regulation of transcription-DNA-templated, immunity and negative regulation of cell proliferation, enriched in cytokine-cytokine receptor interaction signaling pathway, Ras signaling pathway, axon guidance, tumor necrosis factor (TNF) signaling pathway and apoptosis.
We discovered a TAGLN-mediated regulatory network involved in proteinuria progression. These findings provide novel insight to understand the molecular mechanisms underlying the pathogenesis of proteinuria.
蛋白尿是进行性肾功能不全的一个敏感标志。已证实转胶蛋白(TAGLN)参与蛋白尿的病因及足细胞足突的动态变化;然而,TAGLN参与蛋白尿的机制尚不清楚。本研究旨在探讨TAGLN在蛋白尿发生发展中的作用。
从基因表达综合数据库的微阵列表达谱数据集中检测差异表达基因(DEGs),并通过短时序列表达挖掘器分析以对蛋白尿进展中的DEGs进行聚类。使用京都基因与基因组百科全书通路分析来确定前20个富集通路,并构建基因相互作用网络。
总共检测到2409个肾病相关的DEGs以及10612个足细胞足突和蛋白尿相关的DEGs。此外,肾病与足细胞足突之间的76个共同DEGs(25个上调和41个下调)主要参与固有免疫、转录-DNA模板的正调控、免疫以及细胞增殖的负调控,富集于细胞因子-细胞因子受体相互作用信号通路、Ras信号通路、轴突导向、肿瘤坏死因子(TNF)信号通路和凋亡。
我们发现了一个参与蛋白尿进展的TAGLN介导的调控网络。这些发现为理解蛋白尿发病机制的分子机制提供了新的见解。