SRPK1 promotes sepsis-induced acute lung injury via regulating PI3K/AKT/FOXO3 signaling

Abstract

Objective Sepsis is the most common cause of death in intensive care unit. Moreover, sepsis is the leading cause of acute lung injury (ALI). Serine-arginine protein kinase 1 (SRPK1) was demonstrated to promote the development of ALI. However, the potentials of SRPK1 in sepsis-induced ALI are still unknown. This study aimed to investigate the potentials of SRPK1 in sepsis-induced ALI and the underlying mechanisms. Methods Cecal ligation and puncture (CLP) was performed to establish sepsis-induced ALI model in vivo. Primary human pulmonary microvascular endothelial cells (HPMECs) were exposed to lipopolysaccharide (LPS) to construct sepsis-induced ALI model in vitro. Gene expression was detected using western blot and qRT-PCR. The interaction between forkhead box O3 (FOXO3) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was detected using luciferase and Chromatin immunoprecipitation (ChIP) assay. Cellular functions were CCK-8, colony formation, PI staining, and flow cytometry assay. Results SRPK1 was downregulated in patients with sepsis-induced ALI. Overexpression of SRPK1 suppressed the pyroptosis of HPMECs as well as promoted cell proliferation. Additionally, SRPK1 overexpression alleviated sepsis-induced ALI in vivo. SRPK1 activated phosphatidylinositol3-kinase (PI3K) signaling pathways. Blocking the activation of PI3K degraded the cellular functions of HPMECs. Moreover, FOXO3 transcriptionally inactivated NLRP3 and suppressed its mRNA and protein expression. Conclusion Taken together, SRPK1 suppressed sepsis-induced ALI via regulating PI3K/AKT/FOXO3/NLRP3 signaling. SRPK1 may be the potential biomarker for sepsis-induced ALI.