Objective: Sepsis is the most common cause of death in the 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 a sepsis-induced ALI model in vivo. Primary human pulmonary microvascular endothelial cells (HPMECs) were exposed to lipopolysaccharide (LPS) to construct a 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.
Keywords: NLRP3 inflammasome; SRPK1; acute lung injury; pyroptosis; sepsis-induced acute lung injury.