The Journal of surgical research · 2024
Sirtuin 5 Attenuates the Sepsis Induced Lung Injury via Modulation the Succinylation of Serine-Arginine Protein Kinase 1.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Guo Wei, Hu Zhansheng, Ji Lili
Аннотация
INTRODUCTION: Sepsis-induced lung injury represents a clinical syndrome encompassing various forms of acute respiratory failure. Understanding the mechanisms underlying its development is critical for identifying promising therapeutic targets.
METHODS: In this study, both in vitro and in vivo models of septic lung injury were established using a mouse model and the human lung microvascular endothelial cell line HULEC-5a. Quantitative real-time PCR and Western blotting were utilized to measure messenger RNA and protein expression levels. Flow cytometry was employed to assess pyroptosis, and coimmunoprecipitation was used to detect protein-protein interactions. Hematoxylin and eosin staining was performed to evaluate the pathological changes in lung tissues.
RESULTS: Our results demonstrated that Sirtuin 5 expression was significantly downregulated in the blood of patients with septic lung injury, as well as in mice and HULEC-5a cells treated with lipopolysaccharide. SIRT5 suppressed lipopolysaccharide-induced pyroptosis in HULEC-5a cells and septic lung injury in mice. Mechanistically, SIRT5 was shown to directly bind to Serine-Arginine Protein Kinase 1 (SRPK1) and desuccinylate it at lysine residues K588 and K598, thereby reducing its protein stability. Rescue experiments further confirmed that SIRT5 exerts its protective effects against septic lung injury through regulation of SRPK1.
CONCLUSIONS: Collectively, these findings suggested that the SIRT5/SRPK1 signaling pathway may serve as a potential therapeutic target for the treatment of septic lung injury.
METHODS: In this study, both in vitro and in vivo models of septic lung injury were established using a mouse model and the human lung microvascular endothelial cell line HULEC-5a. Quantitative real-time PCR and Western blotting were utilized to measure messenger RNA and protein expression levels. Flow cytometry was employed to assess pyroptosis, and coimmunoprecipitation was used to detect protein-protein interactions. Hematoxylin and eosin staining was performed to evaluate the pathological changes in lung tissues.
RESULTS: Our results demonstrated that Sirtuin 5 expression was significantly downregulated in the blood of patients with septic lung injury, as well as in mice and HULEC-5a cells treated with lipopolysaccharide. SIRT5 suppressed lipopolysaccharide-induced pyroptosis in HULEC-5a cells and septic lung injury in mice. Mechanistically, SIRT5 was shown to directly bind to Serine-Arginine Protein Kinase 1 (SRPK1) and desuccinylate it at lysine residues K588 and K598, thereby reducing its protein stability. Rescue experiments further confirmed that SIRT5 exerts its protective effects against septic lung injury through regulation of SRPK1.
CONCLUSIONS: Collectively, these findings suggested that the SIRT5/SRPK1 signaling pathway may serve as a potential therapeutic target for the treatment of septic lung injury.