Analysis of aquaporin expression in liver with a focus on hepatocytes

Abstract

A deeper understanding of aquaporins (AQPs) expression and transcriptional regulation will provide useful information for liver pathophysiology. We established a complete AQPs mRNA expression profile in human and mouse liver, as well as protein localization of expressed AQPs. Additionally, the modulation of AQPs mRNA levels in response to various agents was determined in human HuH7 cells and in primary culture of mouse hepatocytes. AQP1, AQP3, AQP7, AQP8, and AQP9 mRNA and protein expressions were detected in human liver, while only AQP6 and AQP11 mRNAs were detected. We reported for the first time the localization of AQP3 in Kupffer cells, AQP7 in hepatocytes and endothelial cells, and AQP9 in cholangiocytes. In addition, we confirmed the localization of AQP1 in endothelial cells, and of AQP8 and AQP9 in hepatocytes. On HuH7 cells, we reported the presence of AQP4 mRNA, confirmed the presence of AQP3, AQP7, and AQP11 mRNAs, but not of AQP8 mRNA. On primary culture of murine hepatocytes, AQP1 and AQP7 mRNAs were identified, while the presence of AQP3, AQP8, AQP9, and AQP11 mRNAs was confirmed. At the protein level, murine endothelial liver cells expressed AQP1 and AQP9, while hepatocytes expressed AQP3, AQP7, AQP8, and AQP9, and macrophages expressed AQP3. Dexamethasone, forskolin, AICAR, rosiglitazone, octanoylated, and non-octanoylated ghrelin regulated some AQP expression in primary culture of murine hepatocytes and human HuH7 cells. Additional studies will be required to further assess the role of AQPs expression in human and murine liver and understand the transcriptional regulation of AQPs in hepatocytes under pathophysiological conditions.

Aquaporins in Health and Disease: An Overview Focusing on the Gut of Different Species

“…The involvement of AQPs in the liver must also be considered on the basis of their identification and different distribution in several hepatic cell types, as recently demonstrated [22,41]. The cited authors have charted in the human liver and in both human and mouse hepatocytes the presence of several AQPs providing interesting gene regulation by known drugs/hormones (i.e., dexamethasone, forskolin, rosiglitazone, and ghrelin).…”

“…In particular, the liver strongly expresses at least six AQPs (AQP1, 3, 7, 8, 9, and 11) [22,39,41,57]. Immunohistochemical studies revealed the expression of AQPs in different hepatic cell types, such as in cholangiocytes (AQP1 and AQP7), endothelial cells (AQP1), Kupffer cells (AQP3), and hepatocytes, (AQP7, 8, and 9) [22]. …”

Implications of Aquaglyceroporin 7 in Energy Metabolism

“…AQP7 expression has also been documented in both human [18,67,84,85,86] and mouse [67,84,87] liver. However, others have reported no AQP7 expression in murine [3,14,15,82] and rat [6] liver, and studies of human AQP7 have indicated no [4] or very low levels of AQP7 mRNA in liver [85].…”

“…However, others have reported no AQP7 expression in murine [3,14,15,82] and rat [6] liver, and studies of human AQP7 have indicated no [4] or very low levels of AQP7 mRNA in liver [85]. In human liver, AQP7 has been localized to the cytoplasmic domain of hepatocytes [84,88] and the apical plasma membrane domain of cholangiocytes and endothelial cells [84]. In mice immunohistochemical staining was observed just in the hepatocyte cytoplasmic domain [84].…”

“…In human liver, AQP7 has been localized to the cytoplasmic domain of hepatocytes [84,88] and the apical plasma membrane domain of cholangiocytes and endothelial cells [84]. In mice immunohistochemical staining was observed just in the hepatocyte cytoplasmic domain [84]. In all, the cellular and subcellular localization of AQP7 in liver does not point towards a functional overlap with AQP9, and further studies are needed to clarify the potential role of AQP7 in liver.…”