Identification of ULK1 as a novel mitophagy-related gene in diabetic nephropathy

作者：Yuanyuan Yang, Zhong‐Xiuzi Gao, Zi‐Hui Mao, Dongwei Liu, Zhangsuo Liu, Peng Wu · 发表于：Frontiers in Endocrinology · 年份：2023 · DOI：10.3389/fendo.2022.1079465 · 被引用次数：30 · 研究领域：Autophagy in Disease and Therapy、Chronic Kidney Disease and Diabetes、Ferroptosis and cancer prognosis

Background Accumulating evidence indicates that mitophagy is crucial for the development of diabetic nephropathy (DN). However, little is known about the key genes involved. The present study is to identify the potential mitophagy-related genes (MRGs) in DN. Methods Five datasets were obtained from the Gene Expression Omnibus (GEO) database and were split into the training and validation set. Then the differentially expressed MRGs were screened and further analyzed for GO and KEGG enrichment. Next, three algorithms (SVM-RFE, LASSO and RF) were used to identify hub genes. The ROC curves were plotted based on the hub genes. We then used the CIBERSORT algorithm to assess the infiltration of 22 types of immune cells and explore the correlation between hub genes and immune cells. Finally, the Nephroseq V5 tool was used to analyze the correlation between hub genes and GFR in DN patients. Results Compared with the tubulointerstitium, the expression of MRGs was more noticeably varied in the glomeruli. Twelve DE-MRGs were identified in glomerular samples, of which 11 genes were down-regulated and only MFN1 was up-regulated. GO and KEGG analysis indicated that several enrichment terms were associated with changes in autophagy. Three genes ( MFN1 , ULK1 and PARK2 ) were finally determined as potential hub genes by three algorithms. In the training set, the AUROC of MFN1 , ULK1 and PARK2 were 0.839, 0.906 and 0.842. However, the results of the validation set demonstrated that MFN1 and PA...