ALTERATION OF AKT1-GSK3Β SIGNALING PATHWAY IN TRAUMA HEMORRHAGIC SHOCK PATIENTS.

Area of Science:

• Biomedical Science
• Molecular Biology
• Pathophysiology

Background:

• Trauma hemorrhagic shock (THS) is a leading cause of death globally, often leading to cellular apoptosis, organ dysfunction, and mortality.
• The Akt1-GSK3β signaling pathway is crucial for regulating cell survival and apoptosis, and its dysregulation can exacerbate THS pathology.

Purpose of the Study:

• To investigate the role of the Akt1-GSK3β signaling pathway in the pathophysiology of THS.
• To determine the association between the phosphorylation status of Akt1 and GSK3β and THS severity, immune cell apoptosis, metabolic alterations, inflammation, and mortality.

Main Methods:

• Measurement of Akt1 and GSK3β phosphorylation levels in THS models.
• Correlation analysis of signaling pathway alterations with clinical and pathological parameters of THS.

Main Results:

• Downregulation of phosphorylated Akt1 (pAkt1) and upregulation of phosphorylated GSK3β (pGSK3β) were observed in THS.
• These signaling alterations significantly correlated with increased shock severity, immune cell apoptosis, metabolic dysfunction, inflammation, cytokine storm, hemostasis issues, acidosis, and mortality.
• This study is the first to demonstrate that a dysregulated pAkt1-GSK3β pathway leads to contrasting cell fates, contributing to trauma pathology.

Conclusions:

• The dysregulated Akt1-GSK3β pathway plays a critical role in the pathogenesis of THS, driving cellular dysfunction and mortality.
• Targeting the Akt1-GSK3β signaling pathway presents a novel therapeutic strategy for managing THS.
• Akt activation holds potential for improving survival rates in patients with THS.