Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

Abstract

Sepsis is an inflammatory disorder caused by the host's dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years, it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with a role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at transcriptional, post-transcriptional, translational, and post-translational levels in sepsis by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single-nucleotide polymorphisms in the setting of sepsis.

Keywords: acute respiratory distress syndrome; aquaporin; lnRNA; miRNA; sepsis; single-nucleotide polymorphisms.

Figure 1

Expression and function of aquaporins. AQP1 is expressed in the brain, kidney, lungs, and eyes; AQP2 is predominantly expressed in the kidneys; AQP3 is expressed in the kidneys, the digestive tract, and immune cells; AQP4 is expressed in the central nervous system, kidneys, and digestive tract; and AQP5 is expressed in the lungs and salivary glands. AQP, aquaporin; CSF, cerebrospinal fluid. This figure has been designed using assets from Freepik.com.

Figure 2

Dysregulation of aquaporins in clinical sepsis. AQP1 expression is upregulated in the leukocytes of critically ill septic patients, while serum levels of AQP1 are downregulated. AQP4, AQP5, and AQP9 expression are upregulated in the blood of septic patients. AQP, aquaporin. Green arrows depict upregulation of AQP expression and red arrows depict downregulation. AQP, aquaporin. This figure has been designed using assets from Freepik.com.

Figure 3

Dysregulation of aquaporins in experimental sepsis. (a) Aquaporin expression in animal experimental models following LPS treatment or CLP injection. In LPS-induced experimental models, AQP1, AQP2, AQP3, and AQP5 are downregulated, while AQP9 expression is upregulated. In CLP models, AQP1, AQP2, and AQP5 expression levels are downregulated, while the expression levels of AQP3 and AQP4 are upregulated. (b) Aquaporin expression in in vitro cell models. In PMNs and HPMECs, AQP1 expression is elevated, and in HK2 cells, AQP1 and AQP2 expression levels are downregulated. Green arrows depict upregulation of AQP expression and red arrows depict downregulation. AQP, aquaporin; CLP, cecal ligation and puncture; HK2, human kidney cells 2; HPMEC, human pulmonary microvascular endothelial cells; LPS lipopolysaccharide; PMNs, polymorphonuclear neutrophils. This figure has been designed using assets from Freepik.com.