Overexpression of AQP5 Was Detected in Axillary Sweat Glands of Primary Focal Hyperhidrosis Patients

Du, Qingyou; Lin, Min; Yang, Juhua; Chen, Jianfeng; Tu, Yuan-rong

doi:10.1159/000444081

Cited by 15 publications

(8 citation statements)

References 22 publications

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“…AQP5 is dynamically regulated by multiple mechanisms described by Kitchen et al: (i) at transcriptional/translational level; (ii) by conformational change or “gating” and (iii) by translocation to the membrane in response to a trigger [ 44 ]. In the unstimulated state of the cell, Nejsum et al and Du et al could show AQP5 abundant in the apical and in the basolateral membrane of secretory cells [ 41 , 45 ]. Here, AQP5 was also not specifically connected to the apical membrane of unstimulated secretory coil cells in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

A novel organotypic 3D sweat gland model with physiological functionality

et al. 2017

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Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers. To resemble the in vivo situation as close as possible, we applied the hanging drop cultivation technology regaining most of the markers when cultured in its natural spherical environment. To compare the organotypic 3D sweat gland model versus human sweat glands in vivo, we compared markers relevant for the eccrine sweat gland using transcriptomic and proteomic analysis. Comparing the marker profile, a high in vitro-in vivo correlation was shown. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), muscarinic acetylcholine receptor M3 (CHRM3), Na+-K+-Cl- cotransporter 1 (NKCC1), calcium-activated chloride channel anoctamin-1 (ANO1/TMEM16A), and aquaporin-5 (AQP5) are found at significant expression levels in the 3D model. Moreover, cholinergic stimulation with acetylcholine or pilocarpine leads to calcium influx monitored in a calcium flux assay. Cholinergic stimulation cannot be achieved with the sweat gland cell line NCL-SG3 used as a sweat gland model system. Our results show clear benefits of the organotypic 3D sweat gland model versus 2D cultures in terms of the expression of essential eccrine sweat gland key regulators and in the physiological response to stimulation. Taken together, this novel organotypic 3D sweat gland model shows a good in vitro-in vivo correlation and is an appropriate alternative for screening of potential bioactives regulating the sweat mechanism.

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Section: Discussionmentioning

confidence: 99%

A novel organotypic 3D sweat gland model with physiological functionality

et al. 2017

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“…For instance, sweat shows acidic pH levels, between 4.6 and 5.4 [56], and in the skin the protective sweat acid mantle acidity ranges from 4 to 5.5 [56]; the pH of human stomach is highly acidic, usually from 1 to 2; osteoclasts’ acidic microenvironment below pH 5.5 is critical for the bone resorption [57]; an acidic pH luminal fluid microenvironment is important for sperm maturation [58]. Interestingly, AQP5 was found expressed in sweat glands [59], gastric mucosa [60], bone cells [61], and in the epididymis [58]. In all these tissues, effective mechanisms of water flux regulation induced by pH fluctuations might be advantageous to prevent excessive water reabsorption and control cell volume and shape.…”

Section: Discussionmentioning

confidence: 99%

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

Rodrigues

Mósca

Martins

et al. 2016

IJMS

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Aquaporin-5 (AQP5) is a membrane water channel widely distributed in human tissues that was found up-regulated in different tumors and considered implicated in carcinogenesis in different organs and systems. Despite its wide distribution pattern and physiological importance, AQP5 short-term regulation was not reported and mechanisms underlying its involvement in cancer are not well defined. In this work, we expressed rat AQP5 in yeast and investigated mechanisms of gating, as well as AQP5’s ability to facilitate H2O2 plasma membrane diffusion. We found that AQP5 can be gated by extracellular pH in a phosphorylation-dependent manner, with higher activity at physiological pH 7.4. Moreover, similar to other mammalian AQPs, AQP5 is able to increase extracellular H2O2 influx and to affect oxidative cell response with dual effects: whereas in acute oxidative stress conditions AQP5 induces an initial higher sensitivity, in chronic stress AQP5 expressing cells show improved cell survival and resistance. Our findings support the involvement of AQP5 in oxidative stress and suggest AQP5 modulation by phosphorylation as a novel tool for therapeutics.

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“…Du et al. found an overexpression of aquaporin‐5 in sweat glands using immunohistochemistry and transmission electron microscopy 15 . They speculate that aquaporin‐5 is involved in secretion, at least in axillary sweat glands.…”

Section: Resultsmentioning

confidence: 99%

“…glands using immunohistochemistry and transmission electron microscopy. 15 They speculate that aquaporin-5 is involved in secretion, at least in axillary sweat glands. They try to link the finding to the pathogenetic mechanism of hyperhidrosis.…”

Section: Du Et Al Found An Overexpression Of Aquaporin-5 In Sweatmentioning

confidence: 99%

Progress and lack of progress in hyperhidrosis research 2015–2020. A concise systematic review

Kristensen¹,

Nielsen²

2021

Int J Dermatology

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Hyperhidrosis is excessive sweating that is uncontrollable and occurring regardless of temperature. Quality of life is significantly impaired, and psychiatric comorbidity is common.The objective of the study is to undertake a systematic review of research in the last 5 years regarding hyperhidrosis. Five databases were searched from July 2015 to July 2020 for all research on hyperhidrosis. High-quality research articles were sought for progress in diagnosis, etiology and epidemiology, and use of patient reported outcomes (PROs) as well as randomized clinical trials (RCTs) on any treatment intervention.Outcomes of interest were disease severity, sweat rate, quality of life, patient satisfaction, and adverse events. Trial quality was assessed by the Cochrane risk-of-bias tool. A narrative synthesis was presented. Twenty-nine papers were included in the review: 13 investigational articles, 10 RCTs, three cohort studies, and three reviews. The studies varied in terms of quality, population, intervention, and methods of outcome assessment. The majority were very small studies, and most RCTs were at high risk of bias. Few studies on diagnosis, epidemiology, and etiology were of sufficient quality to be presented.The interventions discussed were iontophoresis, botulinum toxin, anticholinergic medication, curettage, and energy-based technologies. Progress in the diagnostics and etiology of hyperhidrosis is limited with the same being true for treatment. In a 5-year-old systematic review, it was concluded that there was moderate-quality evidence to support the use of botulinum toxin for axillary hyperhidrosis. It was advocated to conduct a trial comparing BTX and iontophoresis for palmar hyperhidrosis. Unfortunately, this has not yet been performed. Hyperhidrosis is still as underserved and under-studied as before.

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Overexpression of AQP5 Was Detected in Axillary Sweat Glands of Primary Focal Hyperhidrosis Patients

Cited by 15 publications

References 22 publications

A novel organotypic 3D sweat gland model with physiological functionality

A novel organotypic 3D sweat gland model with physiological functionality

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

Progress and lack of progress in hyperhidrosis research 2015–2020. A concise systematic review

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