Integrated single-cell RNA sequencing and multi-database analysis reveal THBS2 promotes high glucose-induced mesangial cell oxidative stress and fibrosis in diabetic nephropathy

Single-cell RNA sequencing (scRNA-seq) has provided unprecedented resolution for the study of many diseases, including diabetic nephropathy (DN). However, the effective genes regulating oxidative stress and fibrosis in mesangial cells in DN remain to be revealed. In this study, scRNA-seq and multi-database analysis were used to identify thrombospondin 2 (THBS2) as a key gene in regulating DN progression. The scRNA-seq revealed a total of 6 important cell types in diabetic kidney disease (DKD) from the Gene Expression Omnibus (GEO) database (GSE209781). GO and KEGG analysis showed that the differential genes in mesangial cells of DKD had multi-function and multi-pathway regulation. A total of 4 target genes (ITGB1, THBS2, TIMP1 and COL18A1) were screened by taking the intersection of scRNA-seq (mesangial cells-related genes), GEO database (GSE1009) and GeneCards database (oxidative stress-related genes and renal fibrosis-related genes). THBS2 was overexpressed in high glucose (HG)-induced mesangial cells, and its knockdown inhibited HG-induced mesangial cell oxidative stress and fibrosis. Based on scRNA-seq, multi-database analysis and experimental verification, this study showed that THBS2 might promote HG-induced mesangial cell oxidative stress and fibrosis in DN.