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).
Since the discovery of the AQP1 water channel in 1992 , scientists have sought to understand the function of the 13 aquaporins cloned to date, in the various tissues where they are expressed. In addition to maintaining cell volume, rapid water exchange across cells enables tissues and organs to secrete and/or absorb water as part of their physiological function. AQP1 is detected in the endothelium lining peritoneal capillaries, venules, and small veins . The physiological function of AQP1 in mesothelial cells of the peritoneum could be to secrete water into the peritoneal cavity which, together with glycosaminoglycans and lubricants, facilitates intracoelomic movement of organs. In recent decades, with the increase in the clinical practice of PD, it has been understood that, although in a non-physiological context, the presence of AQP1 in the peritoneal capillaries is a key element ensuring the dialysis process .
An immortalized mesothelial cell line of human peritoneal origin was exploited due to the limitation of primary cell lines which already start to transform at the third passage and did not survive beyond passage six in culture . In fact, human mesothelial cell line (HMC) showed strong Zo-1 tight junctional bands at the cell-cell contacts and express the tetraspan TJ protein occludin, an important determinant for the regulation of paracellular permeability , which is responsible for sealing intercellular TJs . This evidence suggests that the presence of occludin might reduce the paracellular route for water movement. Of note, endogenous expression of TJ proteins Z0-1 and occludin in human peritoneal mesothelial cells has been previously reported  and their role in limiting the paracellular passage of water and solutes has been demonstrated in bovine retinal endothelial cells  and in cultured human peritoneal mesothelial cells .
Epithelial cell polarity is essential for the establishment and maintenance of vectorial transport of ions and fluids that provides the basis for appropriate reabsorptive and secretory function. Interestingly, basolateral but not apical, addition of ouabain (100 µM), significantly reduced the Isc and increased Rt, as assessed by voltage clamp technique. The existence of amiloride-sensitive apical Na+ conductance was previously shown by Ussing experiments in mesothelial cells of human parietal peritoneum, sheep visceral peritoneum, human and sheep parietal pleura . Altogether, these findings in HMC indicated a vectorial transepithelial transport of Na+ and are consistent with the establishment of a polarized monolayer suitable for studying the role of AQP1 water channel in the transmesothelial water transport.
The lack of endogenous expression of AQP1 in HMC is not surprising as it is quite common that, in particular for AQPs, the lack of osmotic challenge in culture condition can downregulate AQPs expression. In fact, it has been reported by several groups that some AQPs, including AQP1, are regulated via osmotic response elements and hypertonicity . The lack of endogenous expression of AQP1 in HMC gave the opportunity to test the rate of transmesothelial water transport in the absence and in the presence of AQP1, given that, besides HgCl2 which is highly toxic to cells, specific drugs that inhibit AQPs function are still lacking.
Indeed, the abundant expression of AQP1 in mesothelial cells in vivo might indicate that these cells need a water channel at the plasma membrane to speed up transcellular water transport, because the paracellular pathway is not per se sufficient to guarantee adequate flow.
It is possible that the minor importance attributed so far to the mesothelium as a functional barrier toward the passage of water may be due, in some cases, to artifacts of the conventional fixation procedure, that induce loss of mesothelial cells, cells shrinkage, and appearance of intercellular gaps , erroneously suggesting that the mesothelium could not be a functional barrier to the passage of water.
In conclusion, (1) in vivo the mesothelium could represent a limiting barrier controlling the transcellular diffusion of water from the submesothelial interstitium to the peritoneal cavity during PD with crystalloid osmolytes and that AQP1 facilitates this process; (2) HMCs can be considered a good in vitro model to study transmesothelial transport phenomena. A number of drugs have been shown to upregulate AQP1 expression in patients . In addition, the notion that AQP1 is upregulated by hypertonicity  but downregulated by glucose degradation products , contained in conventional glucose-based PD solutions, suggests that new solutions with osmotic agents other than glucose, in addition to being more biocompatible , could better preserve the integrity of mesothelium and its AQP1 content, thus resulting in more efficient water UF.