Localization of aquaporin‐5 in sweat glands and functional analysis using knockout mice

Abstract

Sweat secretion involves the transport of salt and water into the lumen of the secretory coil of the sweat gland. By analogy to salivary and submucosal glands, where fluid secretion is aquaporin‐5 (AQP5) dependent, we postulated that aquaporin water channels might facilitate sweat secretion. Immunolocalization with specific antibodies revealed strong expression of AQP5 at the luminal membrane of secretory epithelial cells in sweat glands in mouse paw skin. Novel quantitative methods were developed to compare sweat secretion in wild‐type mice and mice lacking AQP5. Total hindpaw sweat secretion was measured by proton nuclear magnetic resonance of sweat‐derived 1H2O in 2H2O solvent, and sweat secretion from individual glands was measured by real‐time video imaging of sweat droplet formation under oil. Sweat secretion rates after pilocarpine stimulation did not differ in wild‐type mice (0.21 ± 0.03 nl min−1 gland−1) vs. mice lacking AQP5 (0.19 ± 0.04 nl min−1 gland−1). The lack of effect of AQP5 on sweat secretion rate was confirmed by microcapillary collections of sweat from defined regions of mouse paws. Also, as by direct counting of droplets, the number of functional sweat glands was not affected by AQP5 deletion. Sweat gland morphology was similar in wild‐type and AQP5 null mice. From sweat coil geometry and gland secretion rate, the rate of fluid secretion was estimated to be 130 nl min−1 cm−2 of secretory epithelium, substantially lower than that of > 500 nl min−1 cm−2 in kidney proximal tubules and salivary glands, where active fluid absorption or secretion is aquaporin dependent. These results indicate the expression of AQP5 in sweat gland secretory epithelium, but provide direct evidence against its physiological involvement in sweat fluid secretion in mice.

Functions of aquaporins in the eye

“…In each of these systems the rate of transepithelial fluid secretion normalized to epithelial surface area is very high, such that the reduced but non-zero water permeability in AQP deficiency impairs transepithelial osmotic equilibration. In other epithelia, where areanormalized rates of fluid absorption/secretion are much lower, AQPs are not required for transepithelial fluid transport, as found for tear fluid secretion by lacrimal gland , sweat secretion (Song et al, 2002), alveolar fluid absorption (Bai et al, 1999;, and airway fluid absorption . Involvement of AQP-in the reduced tear fluid secretion in Sjogren's syndrome has been suggested (Tsubota et al, 2001), though subsequently refuted (Beroukas et al, 2001).…”

Defective channels lead to an impaired skin barrier

“…This is particularly clear with mutations in connexins, whereby recessive loss-offunction mutations underlie non-syndromic deafness in the absence of an associated skin phenotype (Scott and Kelsell, 2011). This might also be the case for AQP5, as AQP5-null mice have no reported skin abnormalities (Song et al, 2002), although the anatomy of the skin has not been directly studied in these mice. However, mice lacking TRPV3 expression in keratinocytes exhibit a significantly thinner stratum corneum, altered keratinocyte differentiation and impaired barrier function (Cheng et al, 2010), whereas AQP3-null mice retain normal barrier function, but display delayed barrier recovery after disruption .…”

“…Until recently, the expression of AQP5 in the skin was believed to be restricted to the sweat gland cells in the dermis, although its role in sweat secretion is not clear (Nejsum et al, 2002;Song et al, 2002;Inoue et al, 2013). However, we have recently reported the first inherited skin disease associated with aquaporin mutations and have shown that AQP5 is expressed throughout the epidermis, albeit at a much lower level than seen in the sweat glands, with a particularly strong localisation at the plasma membrane in keratinocytes of the stratum granulosum of the palmar epidermis (Fig.…”

Aquaporins: translating bench research to human disease

“…In the various epithelia mentioned above the rates of transepithelial fluid secretion normalized to epithelial surface area are very high, such that the reduced water permeability in AQP deficiency impairs transepithelial osmotic equilibration. In other epithelia having much lower rates of fluid absorption or secretion, including lacrimal gland , sweat gland (Song et al, 2002), alveolus (Bai et al, 1999;Ma et al, 2000a), and airways , AQP deletion does not impair transepithelial fluid transport. Transepithelial water transport is not rate limiting for fluid secretion when rates of fluid secretion are low.…”