Spock2 functions as a key time-series gene of endothelial cells in sepsis-induced cardiomyopathy

Abstract

The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy (SIC), a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture (CLP)-induced septic mice were analyzed at different time points (24, 48 and 72 h) using GSE171546 data. Through weighted gene co-expression network analysis (WGCNA), time series, and differential expression analyses, key time-series differentially expressed genes (DEGs) were identified. Additionally, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint DEGs specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of CLP-induced septic mice. Further, in vitro studies showed that deletion of Spock2 significantly increased LPS-induced apoptosis in human umbilical vein endothelial cells (HUVECs). In conclusion, SPOCK2 expression is increased in septic cardiac endothelial cells and LPS-induced HUVECs and may play a protective role.