Liu Lingyun, Ma Fuzhe, Hao Yuanyuan, Yi Zhengzi, Yu Xiaoxia, Xu Bo, Wei Chengguo, Hu Jinghai
Department of Andrology, The First Hospital of Jilin University, Jilin, China.
Department of Nephrology, The First Hospital of Jilin University, Jilin, China.
Front Med (Lausanne). 2021 Feb 12;7:615306. doi: 10.3389/fmed.2020.615306. eCollection 2020.
Chronic kidney disease (CKD) is a complex disease in which the renal function is compromised chronically. Many studies have indicated the crosstalk between the tubule and the glomerulus in CKD progression. However, our understanding of the interaction of tubular and glomerular injury remains incomplete. In this study, we applied a meta-analysis approach on the transcriptome of the tubules and glomeruli of CKD patients to identify differentially expressed genes (DEGs) signature. Functional analysis of pathways and Gene Ontology found that tubular DEGs were mainly involved in cell assembly and remodeling, glomerular DEGs in cell proliferation and apoptosis, and overlapping DEGs mainly in immune response. Correlation analysis was performed to identify the associated DEGs in the tubules and glomeruli. Secreted protein comparison and verification experiments indicated that WFDC2 from the tubule could downregulate PEX19 mRNA and protein levels at the glomeruli in diabetic kidney disease (DKD). This study revealed the distinctive pathways of the tubules and glomeruli and identified interacted genes during CKD progression.
慢性肾脏病（CKD）是一种肾功能长期受损的复杂疾病。许多研究表明，在CKD进展过程中肾小管与肾小球之间存在相互作用。然而，我们对肾小管和肾小球损伤相互作用的理解仍不完整。在本研究中，我们对CKD患者肾小管和肾小球的转录组应用荟萃分析方法，以鉴定差异表达基因（DEG）特征。对通路和基因本体进行功能分析发现，肾小管DEG主要参与细胞组装和重塑，肾小球DEG主要参与细胞增殖和凋亡，重叠DEG主要参与免疫反应。进行相关性分析以鉴定肾小管和肾小球中的相关DEG。分泌蛋白比较和验证实验表明，来自肾小管的WFDC2可下调糖尿病肾病（DKD）中肾小球的PEX19 mRNA和蛋白水平。本研究揭示了肾小管和肾小球的独特通路，并鉴定了CKD进展过程中的相互作用基因。
