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The Journal of Investigative Dermatology Nov 2018Transepidermal water loss (TEWL) is the most widely used objective measurement for assessing the barrier function of skin in healthy individuals but also patients with... (Review)
Review
Transepidermal water loss (TEWL) is the most widely used objective measurement for assessing the barrier function of skin in healthy individuals but also patients with skin diseases that are associated with skin barrier dysfunction, such as atopic dermatitis. TEWL is the quantity of condensed water that diffuses across a fixed area of stratum corneum to the skin surface per unit time. The water evaporating from the skin is measured using a probe that is placed in contact with the skin surface and contains sensors that detect changes in water vapor density. TEWL can be measured using an open-chamber, unventilated-chamber, or condenser-chamber device. It is a sensitive measure that is affected by properties of the surrounding microclimate such as environmental humidity, temperature, and airflow and should be measured under controlled conditions. TEWL varies significantly across different anatomical sites and also depends on sweat gland activity, skin temperature, and corneocyte properties. Here we describe how to optimally use TEWL measurements as a skin research tool in vivo and in vitro.
Topics: Adaptation, Physiological; Animals; Dermatitis, Atopic; Environmental Exposure; Homeostasis; Humans; Research Design; Skin; Sweat Glands; Tight Junctions; Water; Water Loss, Insensible
PubMed: 30348333
DOI: 10.1016/j.jid.2018.09.001 -
Experimental Dermatology Sep 2015Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are... (Review)
Review
Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca(2+) -dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers - for example InsP3 and Ca(2+) - and downstream ion channels/transporters in the framework of a Na(+) -K(+) -Cl(-) cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid-base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined.
Topics: Animals; Bestrophins; Calcium; Chloride Channels; Eccrine Glands; Humans; Mice; Sodium-Potassium-Chloride Symporters; Sweat; Wnt Signaling Pathway
PubMed: 26014472
DOI: 10.1111/exd.12773 -
Cold Spring Harbor Perspectives in... Feb 2014The human body is covered with several million sweat glands. These tiny coiled tubular skin appendages produce the sweat that is our primary source of cooling and... (Review)
Review
The human body is covered with several million sweat glands. These tiny coiled tubular skin appendages produce the sweat that is our primary source of cooling and hydration of the skin. Numerous studies have been published on their morphology and physiology. Until recently, however, little was known about how glandular skin maintains homeostasis and repairs itself after tissue injury. Here, we provide a brief overview of sweat gland biology, including newly identified reservoirs of stem cells in glandular skin and their activation in response to different types of injuries. Finally, we discuss how the genetics and biology of glandular skin has advanced our knowledge of human disorders associated with altered sweat gland activity.
Topics: Apocrine Glands; Eccrine Glands; Homeostasis; Humans; Regeneration; Signal Transduction; Skin; Stem Cells; Sweat Gland Diseases; Wound Healing
PubMed: 24492848
DOI: 10.1101/cshperspect.a015222 -
Scientific Reports Jan 2022Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia....
Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia. Myoepithelial cells in sweat glands exhibit stemness characteristics and play a major role in sweat gland homeostasis and sweating processes. Previously, we successfully passaged primary myoepithelial cells in spheroid culture systems; however, they could not be maintained for long under in vitro conditions. No myoepithelial cell line has been established to date. In this study, we transduced two immortalizing genes into primary myoepithelial cells and developed a myoepithelial cell line. When compared with primary sweat gland cells, the immortalized myoepithelial cells (designated "iEM") continued to form spheroids after the 4th passage and expressed α-smooth muscle actin and other proteins that characterize myoepithelial cells. Furthermore, treatment with small compounds targeting the Wnt signaling pathways induced differentiation of iEM cells into luminal cells. Thus, we successfully developed an immortalized myoepithelial cell line having differentiation potential. As animal models are not useful for studying human sweat glands, our cell line will be helpful for studying the mechanisms underlying the pathophysiology of sweating disorders.
Topics: Actins; Cell Differentiation; Cell Line, Transformed; Cells, Cultured; Epithelial Cells; Humans; Hyperthermia; Primary Cell Culture; Sweat Glands; Sweating
PubMed: 34997030
DOI: 10.1038/s41598-021-03991-5 -
Journal of Cystic Fibrosis : Official... May 2022CFTR is an anion channel that causes cystic fibrosis (CF) when its activity, equal to channel number x open probability x conductance (n·P·γ) is absent or nearly so.... (Review)
Review
CFTR is an anion channel that causes cystic fibrosis (CF) when its activity, equal to channel number x open probability x conductance (n·P·γ) is absent or nearly so. CFTR modulators increase CFTR activity, but estimates of in vivo efficacy vary. This review shows how values from the simple and widely used sweat chloride test can be calibrated to provide more accurate estimates of CFTR activity as a percent of the average for healthy control (HC) subjects (hereafter 'CFTR activity'). Sweating stimulated by β-adrenergic agonists (β-sweat) is rate-limited by CFTR, producing a near linear, ratio scale of CFTR activity with carriers = 50% and CF = 0% of HC values set = 100%, but the β-sweat assay is difficult to use. Here, sweat chloride is calibrated to CFTR activity by plotting mean sweat chloride values, taken from numerous studies and the CFTR2 database against mean β-sweat rates for CF, carriers and HC. The resulting inverse logarithmic relations indicate that sweat chloride values ≥60 mmol/L occur when CFTR activity is below 1.2% -10% of HC. These are lower than most previous estimates, which resulted from setting nasal potential difference (NPD) as linear rather than logarithmic measures of CFTR activity. Features of the sweat gland coil and duct are used to explain why readouts of CFTR activity are linear for β-sweat and logarithmic for sweat chloride. Sweat chloride values fall steeply for small increments of CFTR activity above zero-the most clinically relevant region. Thus, large health benefits can be achieved by restoring low levels of CFTR activity, especially if this is done before irreversible lung damage. Truncated Abstract: CFTR is an anion channel that causes cystic fibrosis (CF) when its activity, equal to channel number x open probability x conductance (n·P·γ) is absent or nearly so. CFTR modulators increase CFTR activity, but estimates of in vivo efficacy vary. This review shows how values from the sweat chloride test can be calibrated to provide accurate estimates of CFTR activity as a percent of the average for healthy control (HC) subjects. Sweating stimulated by β-adrenergic agonists is rate-limited by CFTR, producing a near linear, ratio scale of CFTR activity, but the assay is difficult to use. Here, sweat chloride is calibrated to CFTR activity by plotting it against mean β-sweat rates for different groups. The resulting logarithmic relations indicate that CF sweat chloride values occur when CFTR activity is below 1.2% -10% of HC, and that large health benefits can be achieved by restoring low levels of CFTR activity if this is done early.
Topics: Adrenergic beta-Agonists; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Mutation; Sweat; Sweat Glands
PubMed: 35184981
DOI: 10.1016/j.jcf.2022.02.001 -
Cell Death & Disease Mar 2019Sweat glands perform a vital thermoregulatory function in mammals. Like other skin components, they originate from epidermal progenitors. However, they have low...
Sweat glands perform a vital thermoregulatory function in mammals. Like other skin components, they originate from epidermal progenitors. However, they have low regenerative potential in response to injury. We have established a sweat gland culture and expansion method using 3D organoids cultures. The epithelial cells derived from sweat glands in dermis of adult mouse paw pads were embedded into Matrigel and formed sweat gland organoids (SGOs). These organoids maintained remarkable stem cell features and demonstrated differentiation capacity to give rise to either sweat gland cells (SGCs) or epidermal cells. Moreover, the bipotent SGO-derived cells could be induced into stratified epidermis structures at the air-liquid interface culture in a medium tailored for skin epidermal cells in vitro. The SGCs embedded in Matrigel tailored for sweat glands formed epithelial organoids, which expressed sweat-gland-specific markers, such as cytokeratin (CK) 18 and CK19, aquaporin (AQP) 5 and αATP. More importantly, they had potential of regeneration of epidermis and sweat gland when they were transplanted into the mouse back wound and claw pad with sweat gland injury, respectively. In summary, we established and optimized culture conditions for effective generation of mouse SGOs. These cells are candidates to restore impaired sweat gland tissue as well as to improve cutaneous skin regeneration.
Topics: Animals; Aquaporin 5; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Collagen; Drug Combinations; Epidermal Cells; Epidermis; Epithelial Cells; Keratin-18; Laminin; Mice; Organoids; Proteoglycans; Regeneration; Skin Transplantation; Stem Cells; Sweat Glands; Tissue Engineering; Wound Healing
PubMed: 30858357
DOI: 10.1038/s41419-019-1485-5 -
Cellular and Molecular Life Sciences :... Jan 2017Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated... (Review)
Review
Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations. More recently, CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease (COPD), and the hyper-responsiveness in asthma, underscoring its fundamental role in whole body health and disease. CFTR regulates many mechanisms in epithelial physiology, such as maintaining epithelial surface hydration and regulating luminal pH. Indeed, recent studies have identified luminal pH as an important arbiter of epithelial barrier function and innate defence, particularly in the airways and GI tract. In this chapter, we will illustrate the different operational roles of CFTR in epithelial function by describing its characteristics in three different tissues: the airways, the pancreas, and the sweat gland.
Topics: Animals; Bicarbonates; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelium; Humans; Immunity, Innate; Lung; Pancreas; Sweat Glands
PubMed: 27714410
DOI: 10.1007/s00018-016-2391-y -
Journal of Applied Physiology... Oct 2019Cholinergic-activated sweating depends on an influx of Ca from extracellular fluid. It is thought that the opening of K channels on secretory epithelial cells...
Cholinergic-activated sweating depends on an influx of Ca from extracellular fluid. It is thought that the opening of K channels on secretory epithelial cells facilitates Ca entry. We examined the hypothesis that tetraethylammonium (TEA)-sensitive K channels participate in sweat production. We used a pre-post experimental design and initiated cholinergic-mediated sweating with intradermal electrical stimulation, monitored local sweat rate (SR) with a small sweat capsule mounted on the skin, and delivered 50 mM TEA via intradermal microdialysis. Local SR was activated by intradermal stimulation frequencies of 0.2-64 Hz, and we generated a sigmoid-shaped stimulus-response curve by plotting the area under the SR-time curve versus log stimulus frequency. Peak local SR was reduced from 0.372 ± 0.331 to 0.226 ± 0.190 mg·min·cm ( = 0.0001) during application of 50 mM TEA, whereas the EC and Hill slopes were not altered. The global sigmoid-shaped stimulus-response curves for control and 50 mM TEA were significantly different ( < 0.0001), and the plateau region was significantly reduced ( = 0.0023) with the TEA treatment. The effect of TEA on peak local SR was similar in male and female subjects. However, we did note a small effect of sex on the shape of the stimulus-response curves during intradermal electrical stimulation. Overall, these data support the hypothesis that cholinergic control of sweat gland activity is modulated by the presence of TEA-sensitive K channels in human sweat gland epithelial cells. The contribution of various potassium channels to the process of cholinergic-mediated human eccrine sweat production is unclear. Using a novel model for cholinergic-mediated sweating in humans, we provide evidence that tetraethylammonium-sensitive K channels (K1.1 and K channels) contribute to eccrine sweat production.
Topics: Adult; Calcium; Eccrine Glands; Female; Humans; Male; Microdialysis; Potassium Channels; Skin; Sweat; Sweating; Tetraethylammonium; Young Adult
PubMed: 31465715
DOI: 10.1152/japplphysiol.00308.2019 -
Journal of Applied Physiology... Aug 2018By combining galvanic skin conductance (GSC), stratum corneum hydration (HYD) and regional surface sweat rate (RSR) measurements at the arm, thigh, back and chest, we...
By combining galvanic skin conductance (GSC), stratum corneum hydration (HYD) and regional surface sweat rate (RSR) measurements at the arm, thigh, back and chest, we closely monitored the passage of sweat from gland to skin surface. Through a varied exercise-rest protocol, sweating was increased slowly and decreased in 16 male and female human participants (25.3 ± 4.7 yr, 174.6 ± 10.1 cm, 71.3 ± 12.0 kg, 53.0 ± 6.8 ml·kg·min). ∆GSC and HYD increased before RSR, indicating pre-secretory sweat gland activity and skin hydration. ∆GSC and HYD typically increased concomitantly during rest in a warm environment (30.1 ± 1.0°C, 30.0 ± 4.7% relative humidity) and only at the arm did ∆GSC increase before an increase in HYD. HYD increased before RSR, before sweat was visible on the skin, but not to full saturation, contradicting earlier hypotheses. Maximal skin hydration did occur, as demonstrated by a plateau in all regions. Post exercise rest resulted in a rapid decrease in HYD and RSR but a delayed decline in ∆GSC. Evidence for reabsorption of surface sweat into the skin following a decline in sweating, as hypothesized in the literature, was not found. This suggests that skin surface sweat, after sweating is decreased, may not diffuse back into the dermis, but is only evaporated. These data, showing distinctly different responses for the three measured variables, provide useful information about the fate of sweat from gland to surface that is relevant across numerous research fields (e.g., thermoregulation, dermatology, ergonomics and material design). NEW & NOTEWORTHY After sweat gland stimulation, sweat travels through the duct, penetrating the epidermis before appearing on the skin surface. We found that only submaximal stratum corneum hydration was required before surface sweating occurred. However, full hydration occurred only once sweat was on the surface. Once sweating reduces, surface sweat evaporation continues, but there is a delayed drying of the skin. This information is relevant across various research fields, including environmental ergonomics, dermatology, thermoregulation, and skin-interface interactions.
Topics: Adult; Body Temperature Regulation; Exercise; Female; Humans; Male; Rest; Skin; Skin Absorption; Skin Physiological Phenomena; Skin Temperature; Sweat; Sweat Glands; Sweating
PubMed: 29745799
DOI: 10.1152/japplphysiol.00872.2017 -
European Journal of Histochemistry : EJH Jan 2023Bromhidrosis has a great negative impact on personal occupation and social psychology. It is not yet clear whether bromhidrosis is caused by apocrine sweat glands or the...
Bromhidrosis has a great negative impact on personal occupation and social psychology. It is not yet clear whether bromhidrosis is caused by apocrine sweat glands or the co-action of apocrine sweat glands and eccrine sweat glands. To distinguish between apocrine sweat glands and eccrine sweat glands, specific antigen markers for apocrine sweat glands and eccrine sweat glands must be found first. In the study, we detected the expression of K7, K18, K19, Na+-K+-2Cl- cotransporter 1 (NKCC1), carbonic anhydrase II (CAII), Forkhead transcription factor a1 (Foxa1), homeobox transcription factor engrailed homeobox1 (En1), gross cystic disease fluid protein-15 (GCDFP-15), mucin-1 (MUC-1), cluster of differentiation 15 (CD15) and apolipoprotein (APOD) in eccrine sweat glands and apocrine sweat glands by immunofluorescence staining. The results showed that K7, K18, K19, Foxa1, GCDFP-15 and MUC-1 were expressed in both apocrine and eccrine sweat glands, CD15 and APOD were only expressed in apocrine sweat glands, and CAII, NKCC1 and En1 were only expressed in eccrine sweat glands. We conclude that CD15 and APOD can serve as specific markers for apocrine sweat glands, while CAII, NKCC1 and En1 can serve as specific markers for eccrine sweat glands to differentiate the two sweat glands.
Topics: Humans; Body Odor; Eccrine Glands; Apocrine Glands; Gene Expression Regulation
PubMed: 36546419
DOI: 10.4081/ejh.2023.3559