S100A4 participates in sepsis-induced endothelial cell inflammatory response and barrier damage by binding to BRD4

BackgroundResearch has shown that S100A4 is upregulated in endothelial cells when exposed to serum from septic patients. This article aims to explore the role of endogenous S100A4 in lipopolysaccharide (LPS)-induced endothelial cells.MethodsA septic HUVECs injury model was established using LPS and transfected with siRNA-S100A4 or Ov-BRD4 plasmid. Targets of S100A4 were predicted using online databases, and immunoprecipitation (IP) was used to verify the binding of S100A4 and targets. Cell viability, levels of apoptosis, and the expression of apoptosis-related proteins were measured to assess cell injury. Transendothelial electrical resistance (TER) and the expression of tight junction proteins were measured to assess cell barrier function. Assessed the inflammatory response by measuring the levels of inflammatory factors, the adhesion of THP-1 monocytes, and the expression of adhesion molecules.ResultsDatabase prediction and IP verification indicated that S100A4 could bind to BRD4 in LPS-induced HUVECs, and the expression of S100A4 and BRD4 was increased in LPS-induced HUVECs. Interference with S100A4 significantly enhanced the cell viability and TER, reduced the apoptosis, TNFα, IL-1β, and IL-6 levels, and THP-1 adhesion number in LPS-treated HUVECs. Additionally, interference with S100A4 upregulated the expression of Bcl2, ZO-1, occludin, and claudin-4 proteins, and downregulated the expression of BRD4, Bax, cleaved caspase-3, ICAM-1, VCAM-1, and E-selectin proteins in LPS-induced HUVECs. However, overexpression of BRD4 significantly attenuated the protective effect of interfering with S100A4 on LPS-induced HUVECs.ConclusionS100A4 is involved in LPS-induced inflammatory response and barrier damage in HUVECs by binding to BRD4.