# Single‐Cell Analysis of Endothelial Cell Injury in IgA Nephropathy

## TL;DR

This study uses single-cell RNA sequencing to show how endothelial cells in the kidney contribute to IgA nephropathy through changes in gene expression involving IL-6 and Rac1.

## Contribution

The study reveals a novel mechanism where IL-6 negatively regulates VE-cad expression in renal endothelial cells via Rac1 in IgA nephropathy.

## Key findings

- IgAN kidney tissues show distinct gene expression patterns in endothelial cells compared to controls.
- IL-6 reduces VE-cad expression in HRGECs, and this effect is mediated through Rac1.
- Rac1 inhibition increases VE-cad expression, suggesting a regulatory role in endothelial injury.

## Abstract

The precise mechanisms responsible for renal injury in IgA nephropathy (IgAN) are not fully understood. Our study employed an extensive scRNA‐seq analysis of kidney biopsies obtained from individuals with IgAN, with a specific emphasis on investigating the involvement of renal endothelial cells.

We obtained data from the Gene Expression Omnibus database and conducted bioinformatics analysis, which included enrichment analysis of differentially expressed genes, AUCell analysis, and high‐dimensional weighted gene co‐expression network analysis (hdWGCNA). The results of these analyses were further validated using human renal glomerular endothelial cells (HRGECs).

The ScRNA‐seq data uncovered notable variations in gene expression between IgAN and control kidney tissues. The enrichment analysis using AUCell demonstrated a high presence of adhesion molecules and components related to the mitogen‐activated protein kinase signaling pathway within the renal endothelial cells. Furthermore, through hdWGCNA analysis, it was discovered that interleukin (IL)‐6, Rac1, and cadherin exhibited associations with the renal endothelial cells. Stimulation of HRGECs with IL‐6/IL‐6 receptor resulted in a significant reduction in VE‐cad expression while inhibiting Rac1 led to a substantial decrease in Rac1‐GTP levels and an increase in VE‐cad expression.

This study presents novel findings regarding the contribution of renal endothelial cells to the development of IgAN, as it demonstrates that IL‐6 negatively regulates VE‐cad expression in HRGECs via Rac1. These results highlight the significant involvement of renal endothelial cells in the pathogenesis of IgAN.

This study presents novel findings regarding the contribution of renal endothelial cells to the development of IgAN, as it demonstrates that IL‐6 negatively regulates VE‐cad expression in HRGECs via Rac1. These results highlight the significant involvement of renal endothelial cells in the pathogenesis of IgAN.