Aquaporins in sepsis- an update

Area of Science:

• Molecular Biology
• Immunology
• Pathophysiology

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated immune response to infection.
• Aquaporins (AQPs) are membrane proteins crucial for water and solute transport, with emerging roles in sepsis beyond fluid balance.
• AQPs are increasingly recognized for their involvement in immune modulation and metabolic regulation during sepsis.

Purpose of the Study:

• To review the emerging roles of aquaporins in immune metabolism and their therapeutic potential in sepsis.
• To explore AQP contributions to inflammatory responses, organ protection, and immune cell metabolic shifts.
• To highlight AQP involvement in renal, pulmonary, cardiac, and gastrointestinal functions during sepsis.

Main Methods:

• Review of recent studies on aquaporin function in sepsis pathophysiology.
• Analysis of AQP roles in immune cell metabolism, including glycerol transport and glycolysis.
• Examination of AQP involvement in immune cell migration, activation, and inflammatory signaling pathways (e.g., TLR4, PI3K, NF-κB).

Main Results:

• Aquaglyceroporins (e.g., AQP3, AQP7, AQP9) are pivotal in immune cell metabolism, facilitating glycerol transport to fuel glycolysis.
• AQPs regulate key immune functions, including neutrophil migration (AQP9) and inflammatory modulation (AQP3, AQP1).
• AQP modulation (inhibition or regulation via non-coding RNAs) shows therapeutic promise in reducing inflammation, oxidative stress, and organ damage in sepsis models.
• Altered AQP expression (e.g., AQP1, AQP3, AQP5) correlates with sepsis severity and outcomes, suggesting biomarker potential.

Conclusions:

• Aquaporins play a multifaceted role in sepsis, significantly impacting immune metabolism and inflammation.
• Targeting AQPs presents a promising therapeutic strategy for mitigating sepsis-induced organ damage and enhancing patient survival.
• Further research into AQP metabolic and immune functions is crucial for clinical translation of targeted therapies.