Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link

Abstract

BackgroundIgA nephropathy (IgAN) is an autoimmune disease that affects people of any age and is an important cause of end-stage renal disease. However, the pathogenesis and pathophysiology of IgAN is not clear. This article aimed to explore the immune-mediated inflammation and genetic mechanisms in IgAN.MethodsThe transcriptome sequencing data of IgAN glomeruli in the Gene Expression Omnibus database were downloaded. Single-sample gene set enrichment analysis was used to estimate the immune microenvironment of the merged microarray data and GSE141295. IgAN samples were divided into two clusters by cluster analysis. “limma” and “DEseq2” package in R were used to identify differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules related to inflammation in IgAN. R software package “clusterProfiler” was used for enrichment analysis, whereas Short Time-Series Expression Miner (STEM) analysis was used to identify the trend of gene expression. Machine-learn (ML) was performed using the shiny app. Finally, Drug Signatures Database (DSigDB) was used to identify potential molecules for treating IgAN.ResultsThe infiltration of macrophages in IgAN glomeruli was increased, whereas CD4+ T cells, especially inducedregulatory T cells (iTregs) were decreased. A total of 1,104 common DEGs were identified from the merged data and GSE141295. Brown module was identified to have the highest inflammatory correlation with IgAN using WGCNA, and 15 hub genes were screened from this module. Among these 15 hub genes, 14 increased with the severity of IgAN inflammation based on STEM analysis. Neural network (nnet) is considered as the best model to predict the severity of IgAN. Fucose identified from DSigDB has a potential biological activity to treat IgAN.ConclusionThe increase of macrophages and the decrease of iTregs in glomeruli represent the immune-mediated inflammation of IgAN, and fucose may be a potential therapeutic molecule against IgAN because it affects genes involved in the severe inflammation of IgAN.

Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease

“…However, at the present time, its exogenous administration was also identified via a neural network model using the Drug Signatures Database as a candidate for treating severe inflammation in IgAN by reducing the deposition of complement C3 [ 44 ], and its administration was also found to alleviate intestinal epithelial damage via upregulating FUT2, impeding oxidative stress, mitochondrial dysfunction, and cell apoptosis [ 45 ]. In kidney transplants, it has been studied as a decoy molecule, significantly reducing ischemia reperfusion injury [ 46 ].…”

Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning

“…Subsequently, the results were visualized using Cytoscape software. We used the Enrichr platform (https://amp.pharm.mssm.edu/ Enrichr/) (18) to access the DSigDB database (19) for potential drug prediction.…”

The role of the glycome in symbiotic host-microbe interactions

“…On the host side, fucosylation may modulate antitumor immunity and, therefore, could be considered as one of the immunotherapeutic approaches in the treatment of cancer ( Adhikari et al 2022 ). Fucose itself could be also considered as a potential therapeutic molecule in autoimmune diseases with the immune-mediated inflammation such as IgA nephropathy ( Qing et al 2022 ). L-fucose treatment ameliorates DSS-induced colonic inflammation and intestinal epithelial injury via accelerating the proliferation of intestinal stem cells ( Tan et al 2022 ).…”