Diabetes, Metabolic Syndrome and Obesity (Dec 2022)
Expression of Ferroptosis-Related Genes is Correlated with Immune Microenvironment in Diabetic Kidney Disease
Abstract
Lihua Ni,1,* Jingyuan Cao,2,* Cheng Yuan,3 Le-Ting Zhou,4 Xiaoyan Wu1 1Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People’s Republic of China; 3Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyan Wu; Le-Ting Zhou, Email [email protected]; [email protected]: This study aims to explore the correlation between ferroptosis and immune microenvironment (IME) in diabetic kidney disease (DKD) to provide a new clue for exploring the underlying molecular mechanisms.Methods: Corresponding RNA data of DKD patients were downloaded from GEO databases. The weighted gene co-expression network analysis (WGCNA) was used to construct the network, and the selected hub genes, then, overlapped with ferroptosis-related genes (FRGs) from FerrDb. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, TIMER and ssGSEA analyses were applied to determinate the IME and immune status. Functional analyses including GO, KEGG and GSEA were conducted to elucidate the underlying mechanisms.Results: Two molecular subtypes were identified based on the expression of FRGs. ESTIMATE algorithm revealed that there were significant differences in ESTIMATE score between these two clusters of DKD patients, with no significant difference found in stromal score and immune score. In addition, TIMER algorithm indicated there was a significant difference in the degree of T cell infiltration. The ssGSEA algorithm showed immunity was mainly concentrated in thick ascending limb and distal convoluted tubule in adult kidney. GO, KEGG and GSEA analyses revealed that the differentially expressed genes (DEGs) were mainly enriched in immune and metabolism associated pathways.Conclusion: The ferroptosis may be induced by dysregulation of IME, thereby accelerating the progression of DKD. Our work could be applied to provide a new clue for exploring the underlying molecular mechanisms and sheds novel light on the therapy strategy of DKD.Keywords: diabetic kidney disease, DKD, ferroptosis, immune microenvironment, IME, metabolism
