A Systematic Characterization of Aquaporin-9 Expression in Human Normal and Pathological Tissues

Abstract

SummaryAQP9 is known to facilitate hepatocyte glycerol uptake. Murine AQP9 protein expression has been verified in liver, skin, epididymis, epidermis and neuronal cells using knockout mice. Further expression sites have been reported in humans. We aimed to verify AQP9 expression in a large set of human normal organs, different cancer types, rheumatoid arthritis synovial biopsies as well as in cell lines and primary cells. Combining standardized immunohistochemistry with high-throughput mRNA sequencing, we found that AQP9 expression in normal tissues was limited, with high membranous expression only in hepatocytes. In cancer tissues, AQP9 expression was mainly found in hepatocellular carcinomas, suggesting no general contribution of AQP9 to carcinogenesis. AQP9 expression in a subset of rheumatoid arthritis synovial tissue samples was affected by Humira, thereby supporting a suggested role of TNFα in AQP9 regulation in this disease. Among cell lines and primary cells, LP-1 myeloma cells expressed high levels of AQP9, whereas low expression was observed in a few other lymphoid cell lines. AQP9 mRNA and protein expression was absent in HepG2 hepatocellular carcinoma cells. Overall, AQP9 expression in human tissues appears to be more selective than in mice. (J Histochem Cytochem 64:287-300, 2016)

Aquaporins in the Spinal Cord

“…Furthermore, the observed expression level in mouse brain is about six times lower compared to rat brain [52]. Recent systemic data gathered from human samples revealed that AQP9 mRNA is expressed at very low levels in brain [53]. Despite some progress made for clarifying the true expression of AQP9 in the brain, the data on the potential presence and localization of this aquaglyceroporin in spinal cord remain limited.…”

Expression of the aquaglyceroporin HC ‐9 in a freeze‐tolerant amphibian that accumulates glycerol seasonally

“…; Lindskog et al. ) and some (rainbow smelt; Hall et al ) but not all (zebrafish; Hamdi et al ) fishes.…”

“…), but an assessment of immunohistological staining patterns in human tissues found AQP9 protein expression predominately in hepatocytes, with little to no conclusive expression among the other 82 cell types analyzed (Lindskog et al. ).…”

“…* indicates a condition with a P < 0.05 compared by one-way ANOVA to the band from the warm-acclimated condition. , as well as in mammals (Rojek et al 2008;Lindskog et al 2016) and some (rainbow smelt; Hall et al 2015) but not all (zebrafish; Hamdi et al 2009) fishes. Despite detection of AQP9 mRNA widely across tissues, the expression of AQP9 protein may be more tissue selective.…”

The Human Protein Atlas – an important resource for basic and clinical research

“…The thorough exploration of protein expression using highthroughput immunohistochemical staining in a tissue microarray format provides a detailed map of where a particular protein is expressed, in contrast to many publications analyzing only a few organs. One such example is a recent study on the protein Aquaporin-9 [13], where a systematic evaluation using an integrated omics approach within the Human Protein Atlas project could confidently confirm protein expression only in human hepatocytes, while previous studies have reported various expression sites, often with contradictory results. As Aquaporin-9 has been suggested as a potential drug target in type 2 diabetes, the tissue specificity provides important information from a safety perspective.…”