Nan-Nan Zhang, Yi Zhu, Qiu-Yan Huang, Fei Hu, Jun Li, Xia Yang
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引用次数: 0
Abstract
Objective: Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease (DKD). However, investigations of immune cell-related ferroptosis genes (ICRFGs) in the context of DKD are insufficient. This study aimed to identify ICRFGs relevant to DKD and screen related inhibitors.
Methods: In this study, two DKD datasets from the GEO database were utilized. We adopted the ESTIMATE algorithm to generate microenvironment scores. The CIBERSORT and WGCNA methods were employed to identify immune-related differentially expressed genes (DEGs). The common ICRFGs were derived through a Venn diagram. We employed random forest, LASSO, K-M survival, receiver operating characteristic (ROC) curve, clinical relevance, and Spearman correlation analyses to select hub ICRFGs further. Immunohistochemical experiments were also performed to validate the expression. Additionally, we utilized the Selleck database to obtain ferroptosis-related compounds and used USCF Chimera 1.14 to minimize energy, combined with molecular dynamics (MD) simulations to explore possible ferroptosis inhibitors.
Results: Immunohistochemical analysis revealed that arachidonate 5-lipoxygenase (ALOX5) was significantly highly expressed in the db/db group. Clinical correlation and K-M survival analyses confirmed ALOX5 as the most crucial ICRFG in DKD. Furthermore, ALOX5 was significantly enriched in the terms ECM-receptor interaction, regulation of chemokine production, and regulation of the inflammatory response. A positive correlation was observed between ALOX5 and M1 macrophages, γδ T cells, and monocytes. Moreover, virtual screening and MD revealed NSC348884, salvianolic acid B, and deltarasin as potential ferroptosis inhibitors in combination with ALOX5.
Conclusion: We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients.
期刊介绍:
Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.