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. 2024 Jan 19;25(2):1209.
doi: 10.3390/ijms25021209.

AQP3 and AQP9-Contrary Players in Sepsis?

Patrick Thon  1 , Tim Rahmel  1 , Dominik Ziehe  1 , Lars Palmowski  1 , Britta Marko  1 , Hartmuth Nowak  1   2 , Alexander Wolf  1 , Andrea Witowski  1 , Jennifer Orlowski  1 , Björn Ellger  3 , Frank Wappler  4 , Elke Schwier  5 , Dietrich Henzler  5 , Thomas Köhler  5 , Alexander Zarbock  6 , Stefan Felix Ehrentraut  7 , Christian Putensen  7 , Ulrich Hermann Frey  8 , Moritz Anft  9 , Nina Babel  9 , Barbara Sitek  1 , Michael Adamzik  1 , Lars Bergmann  1 , Matthias Unterberg  1 , Björn Koos  1 , Katharina Rump  1 ; SepsisDataNet.NRW Research Group
Affiliations

AQP3 and AQP9-Contrary Players in Sepsis?

Patrick Thon et al. Int J Mol Sci. .

Abstract

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest. In this study, we tested the hypothesis that these aquaporins are expressed in the blood cells of septic patients and impact sepsis survival. Clinical data, routine laboratory parameters, and blood samples from septic patients were analyzed on day 1 and day 8 after sepsis diagnosis. AQP expression and cytokine serum concentrations were measured. AQP3 mRNA expression increased over the duration of sepsis and was correlated with lymphocyte count. High AQP3 expression was associated with increased survival. In contrast, AQP9 expression was not altered during sepsis and was correlated with neutrophil count, and low levels of AQP9 were associated with increased survival. Furthermore, AQP9 expression was an independent risk factor for sepsis lethality. In conclusion, AQP3 and AQP9 may play contrary roles in the pathophysiology of sepsis, and these results suggest that AQP9 may be a novel drug target in sepsis and, concurrently, a valuable biomarker of the disease.

Keywords: AQP3; AQP9; aquaporins; critical illness; mortality; sepsis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
mRNA Expression of AQP3 and AQP9 in the whole blood samples of septic patients, measured by qRT-PCR. AQP3 and AQP9 mRNA was measured in cDNA samples relative to the housekeeping gene β-actin (ACTB). n = 87, unpaired t-Test, **** p < 0.0001.
Figure 2
Figure 2
mRNA AQP expression in the whole blood samples of septic patients on day 1 and day 8 after sepsis diagnosis measured by qRT-PCR. AQP3 and AQP9 mRNA were measured in cDNA samples relative to the housekeeping gene β-actin (ACTB). n = 87 (day 1); n = 36 (day 8), Mann–Whitney test, **** p < 0.0001, ns = not significant.
Figure 3
Figure 3
Pearson Correlation analysis of AQP3 mRNA expression with cell counts (cells per µL blood) (n = 24 neutrophils; n = 25 lymphocytes; and n = 49 leucocytes); dots: the two variables of the same patient, line: correlation line of all patients.
Figure 4
Figure 4
Pearson Correlation analysis of AQP9 mRNA expression with cell counts (cells per µL blood) (n = 19 neutrophils; n = 29 lymphocytes; and n = 29 classical monocytes); dots: the two variables of the same patient, line: correlation line of all patients.
Figure 5
Figure 5
Pearson Correlation analysis of AQP3 and AQP9 mRNA with cytokines on day 1 (pg/µL) (n = 75 for correlations with AQP3 and n = 41 for correlations with AQP9); dots: the two variables of the same patient, line: correlation line of all patients.
Figure 6
Figure 6
Pearson Correlation analysis of AQP3 and AQP9 mRNA with cytokines on day 8 (pg/µL) (n = 30 for correlations with AQP3 and n = 23 for correlations with AQP9); dots: the two variables of the same patient, line: correlation line of all patients.
Figure 7
Figure 7
Kaplan–Meier analysis of 30-day sepsis survival, with septic patients stratified using cut-off values of AQP3 and AQP9 mRNA expression relative to ACTB. Cut-off values were determined using ROC analysis and the Youden index. The patient cohort was divided by cut-off value: the cut-off for AQP3 was 0.00223 (n = 33), and that for AQP9 was 0.088078 (n = 27). Green line: patients exceeding the cut-off; blue line: patients falling below the cut-off.
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