Abstract
We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.
Highlights
We previously reported that the water channel aquaporin 1 (AQP1) is abundantly expressed in human peritoneal mesothelial cells, released through exosomes in the dialysis fluid during peritoneal dialysis (PD), and its abundance in the perfusate well correlates with dialysis efficiency [17]
Our results indicate that the presence of AQP1 in mesothelial cells is associated with an increase in the rate of osmotic water transport, suggesting that AQP1 may play the same role in mesothelium in vivo
Since the discovery of the AQP1 water channel in 1992 [29], scientists have sought to understand the function of the 13 aquaporins cloned to date, in the various tissues where they are expressed
Summary
The peritoneal membrane is considered as the first-line barrier that provides a protective, non-adhesive surface on the abdominal cavity and organs. The peritoneal membrane is structured by a layer of squamous-like and cuboidal ciliated mesothelial cells with microvilli and cell-cell junctional complexes, an interstitium containing bundles of collagen and mucopolysaccharides, and a dense network of capillaries, blood vessels, and lymphatics [1]. Mesothelial cells are mesodermal in origin and possess both epithelial and mesenchymal features, which allows for them to play numerous and important functions. In addition to providing a protective and friction-free interface for the free movement of opposing organs and tissues, the mesothelium is involved in initiation and resolution of inflammation, tissue repair, release of factors to promote both the deposition and clearance of fibrin, and antigen presentation [2]
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