Human Eccrine Sweat Research Articles

Amino acid composition, including key derivatives of eccrine sweat: potential biomarkers of certain atopic skin conditions

The free amino acid (AA) composition of eccrine sweat is different from other biological fluids, for reasons which are not properly understood. We undertook the detailed analysis of the AA composition of freshly isolated pure human eccrine sweat, including some of the key derivatives of AA metabolism, to better understand the key biological mechanisms governing its composition. Eccrine sweat was collected from the axillae of 12 healthy subjects immediately upon formation. Free AA analysis was performed using an automatic AA analyser after ninhydrin derivatization. Pyrrolidine-5-carboxylic acid (PCA) and urocanic acid (UCA) levels were determined using GC/MS. The free AA composition of sweat was dominated by the presence of serine accounting for just over one-fifth of the total free AA composition. Glycine was the next most abundant followed by PCA, alanine, citrulline and threonine, respectively. The data obtained indicate that the AA content of sweat bears a remarkable similarity to the AA composition of the epidermal protein profilaggrin. This protein is the key source of free AAs and their derivatives that form a major part of the natural moisturizing factor (NMF) within the stratum corneum (SC) and plays a major role in maintaining the barrier integrity of human skin. As perturbations in the production of NMF can lead to abnormal barrier function and can arise as a consequence of filaggrin genotype, we propose the quantification of AAs in sweat may serve as a non-invasive diagnostic biomarker for certain atopic skin conditions, that is, atopic dermatitis (AD).

Endocannabinoids Regulate Growth and Survival of Human Eccrine Sweat Gland–Derived Epithelial Cells

The functional existence of the emerging endocannabinoid system (ECS), one of the new neuroendocrine players in cutaneous biology, is recently described in the human skin. In this study, using human eccrine sweat gland-derived immortalized NCL-SG3 model cells and a wide array of cellular and molecular assays, we investigated the effects of prototypic endocannabinoids (anandamide, 2-arachidonoylglycerol) on cellular functions. We show here that both endocannabinoids dose-dependently suppressed proliferation, induced apoptosis, altered expressions of various cytoskeleton proteins (e.g., cytokeratins), and upregulated lipid synthesis. Interestingly, as revealed by specific agonists and antagonists as well as by RNA interference, neither the metabotropic cannabinoid receptors (CB) nor the "ionotropic" CB transient receptor potential ion channels, expressed by these cells, mediated the cellular actions of the endocannabinoids. However, the endocannabinoids selectively activated the mitogen-activated protein kinase signaling pathway. Finally, other elements of the ECS (i.e., enzymes involved in the synthesis and degradation of endocannabinoids) were also identified on NCL-SG3 cells. These results collectively suggest that cannabinoids exert a profound regulatory role in the biology of the appendage. Therefore, from a therapeutic point of view, upregulation of endocannabinoid levels might help to manage certain sweat gland-derived disorders (e.g., tumors) characterized by unwanted growth.

Blocking the beta-adrenergic system does not affect sweat gland function during heat acclimation

The purpose of the current study was to test the hypothesis that the beta-adrenergic innervation of the human eccrine sweat gland facilitates greater sweat production following heat acclimation. Eight healthy subjects (mean ± SD age: 25.1 ± 4.1 years, weight: 79.0 ± 16.1 kg, and VO(2)max: 48.5 ± 8.0 ml/kg/min) underwent active heat acclimation by walking at 40% of their VO(2)max for 8 days (90 min a day) in an environmental chamber (35.3 ± 0.8°C and 40.2 ± 2.1% rH). To test the hypothesis, the adrenergic component of sweat gland innervation was inhibited by continuously administering a 0.5% solution of the beta-adrenergic antagonist propranolol via iontophoresis to a 5 cm(2) area of one forearm during each 90-min exercise bout. The opposing control forearm underwent iontophoresis with a saline solution. Following heat acclimation, mean sweat rate in the inhibited and control forearm was 0.47 ± 0.30 mg/cm(2)/min and 0.44 ± 0.25mg/cm(2)/min, respectively. Findings of the current study fail to support the hypothesis that adrenergic innervation facilitates human eccrine sweat gland function during heat acclimation, as no significant differences in sweating were observed. In light of the above, the physiological significance of the dual cholinergic and adrenergic innervation of the eccrine sweat gland has yet to be determined.

Noninvasive Galvanic Skin Sensor for Early Diagnosis of Sudomotor Dysfunction: Application to Diabetes

Sudomotor dysfunction is a major clinical manifestation of diabetic autonomic neuropathy and is an early sign of prediabetes. SUDOSCAN™, a noninvasive and quick method was developed to assess sudomotor function based on measurement of the electrical current response of the skin when different rectangular pulses of low voltage amplitudes are applied on nickel electrodes. Electrochemical skin conductance is then calculated from the resulting voltage and the generated current. This leads to an accurate noninvasive way to predict dysglycemia, including type II diabetes, without fasting requirement due to the sensitivity of Ni electrodes to human eccrine glands sweat.

Hepatocyte growth factor promoting the proliferation of human eccrine sweat gland epithelial cells is relative to AKT signal channel and β-catenin

Hepatocyte growth factor (HGF) is a multi-effective molecule, playing important roles in organ growth, tumorigenesis and trauma healing. This experiment aims at studying the promoting function of HGF on the proliferation of human eccrine sweat gland epithelial cells (hESGc) and its relative signal channels. After HGF at different concentrations were added into cells, MTT was adopted to detect the cell proliferations, Annexin-V/PI the cell apoptosis, and Westernblot the expressions of p-AKT, AKT, p-ERK, p-GSK3β, p-IKBα, and β-catenin in hESGc. After adding siRNA c-Met to block HGF or LY294002 to inhibit p-AKT, we used MTT to detect the proliferation of hESGc and Westernblot to detect the expression of β-catenin. As a result, 20-40 ng/mL HGF could promote the proliferation of hESGc and inhibit its apoptosis. HGF could promote the expressions of p-AKT1/2/3, p-ERK, p-GSK3β, p-IKBα, and β-catenin. The additions of siRNA c-Met to block HGF or LY294002 to inhibit p-AKT could downregulate β-catenin and inhibit the proliferation promotion caused by HGF. Consequently, we concluded HGF can promote the proliferation of human eccrine sweat gland epithelial cells, which is relative to AKT signal channel and β-catenin.

Matrigel-Induced Tubular Morphogenesis of Human Eccrine Sweat Gland Epithelial Cells

Human eccrine sweat glands are tubule-structured glands of the skin that are vital in thermoregulation, secretion, and excretion of water and electrolytes. A study of tubular morphogenesis in vitro would facilitate the development of a tissue engineering model for eccrine sweat glands and other tubule-structured glands. Matrigel, a basement membrane matrix, has been shown to promote differentiation and morphogenesis of many different cell types, including tubular cells. This study investigated the growth, differentiation, and tubular morphogenesis of human eccrine sweat gland epithelial cells cultured in Matrigel. Human eccrine gland epithelial cells were isolated and cultured in vitro. The cell growth in Matrigel was evidenced by the formation of cell clusters, which were observed under an inverted microscope. The internal structure of the cell clusters was further investigated by hematoxylin-eosin (HE) staining and confocal laser scanning microscopy (CLSM) of propidium iodide-stained nuclei. The results demonstrated that although on a plastic surface or in a collagen gel the cells could not form tubular structures, they formed tubular structures when cultured in Matrigel. Consequently, we conclude that Matrigel can promote tubular morphogenesis of human eccrine sweat gland epithelial cells.

Low abundance of sweat duct Cl- channel CFTR in both healthy and cystic fibrosis athletes with exceptionally salty sweat during exercise.

To understand potential mechanisms explaining interindividual variability observed in human sweat sodium concentration ([Na(+)]), we investigated the relationship among [Na(+)] of thermoregulatory sweat, plasma membrane expression of Na(+) and Cl(-) transport proteins in biopsied human eccrine sweat ducts, and basal levels of vasopressin (AVP) and aldosterone. Lower ductal luminal membrane expression of the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR) was observed in immunofluorescent staining of sweat glands from healthy young adults identified as exceptionally "salty sweaters" (SS) (n = 6, P < 0.05) and from patients with cystic fibrosis (CF) (n = 6, P < 0.005) compared with ducts from healthy young adults with "typical" sweat [Na(+)] (control, n = 6). Genetic testing of healthy subjects did not reveal any heterozygotes ("carriers") for any of the 39 most common disease-causing CFTR mutations in the United States. SS had higher baseline plasma [AVP] compared with control (P = 0.029). Immunostaining to investigate a potential relationship between higher plasma [AVP] (and sweat [Na(+)]) and ductal membrane aquaporin-5 revealed for all groups a relatively sparse and location-dependent ductal expression of the water channel with localization primarily to the secretory coil. Availability of CFTR for NaCl transport across the ductal membrane appears related to the significant physiological variability observed in sweat salt concentration in apparently healthy humans. At present, a heritable link between healthy salty sweaters and the most prevalent disease-causing CFTR mutations cannot be established.

Human Eccrine Sweat Gland Cells Can Reconstitute a Stratified Epidermis

Eccrine sweat glands are generally considered to be a possible epidermal stem cell source. Here we compared the multilayered epithelia formed by epidermal keratinocytes and those formed by eccrine sweat gland cells. We demonstrated both in vitro and in vivo the capability of human eccrine sweat gland cells to form a stratified interfollicular epidermis substitute on collagen hydrogels. This is substantiated by the following findings: (1) a stratified epidermis consisting of 10-12 cell layers is formed by sweat gland cells; (2) a distinct stratum corneum develops and is maintained after transplantation onto immuno-incompetent rats; (3) proteins such as filaggrin, loricrin, involucrin, envoplakin, periplakin, and transglutaminases I and III match with the pattern of the normal human skin; (4) junctional complexes and hemidesmosomes are readily and regularly established; (5) cell proliferation in the basal layer reaches homeostatic levels; (6) the sweat gland-derived epidermis is anchored by hemidesmosomes within a well-developed basal lamina; and (7) palmo-plantar or mucosal markers are not expressed in the sweat gland-derived epidermis. These data suggest that human eccrine sweat glands are an additional source of keratinocytes that can generate a stratified epidermis. Our findings raise the question of the extent to which the human skin is repaired and/or permanently renewed by eccrine sweat gland cells.

A new way for isolation and cultivation of sweat gland ductal cells from human split-thickness skin in vitro

To explore a new method of isolation and culture of eccrine sweat gland ductal cells from human split-thickness skin graft in vitro. Human split-thickness skin graft which was presented by volunteer (n = 10) was digested with type II collagenase, and then sweat gland duct were isolated from the split-thickness skin graft, primary cultures were incubated at 37 degrees C in humidified atmosphere of 5% CO2, 95% O2. The cultured eccrine sweat gland ductal cells were identified by analysis CEA, CK8, CK18, CK19 antigens expression with flow cytometry, RT-PCR and Western Blot, and by detecting the electrophysiology with whole cell patch clamp technology. The isolated eccrine sweat gland ductal cells could grow by adhering to the wall, proliferate in vitro after 48 h of adhering to the wall, and confluens after 2 - 4 weeks of adhering to the wall. The FACs analysis showed the expression of CEA was (90.26 +/- 1.12)%, (89.70 +/- 1.43)%, and CK8 was (94.41 +/- 1.84)%, (93.65 +/- 1.63)% in primary cultured sweat gland ductal cells and primary cultured eccrine sweat gland cells, respectively, and there is no significant difference between the two groups (P > 0.05). Immunocytochemistry staining showed CEA, CK8, CK18, CK19 was positive in sweat gland duct cells, RT-PCR revealed that CEA, CK8, CK18 and CK19 gene expression in sweat gland ductal cells, and Western Blot analysis showed the expression of CEA brand, CK8 brand, CK18 brand, and CK19 brand in sweat gland ductal cells, patch clamp indicated that this cells has distinct amiloride sensitive Na(+) channels. The cultured human eccrine sweat gland duct cells in vitro display the markers and biological characteristics of sweat gland epithelial lineage, and this method of digest the split-thickness skin graft to get the sweat gland duct cells is better than classical dissect sweat gland under dissect microscope.

Aerobic exercise training increases maximal in vivo cholinergic responsiveness but not sensitivity of eccrine sweat glands

Aerobic exercise training increases maximal sweat capacity and sweat responses at a given internal temperature. However, the mechanisms underlying these effects are unknown. The purpose of this study was to determine if aerobic exercise training improves in vivo cholinergic sensitivity and responsiveness of eccrine sweat glands. Eleven previously sedentary subjects were tested before and after 8 weeks of aerobic training consisting of 4 bouts of exercise per week that elicited an ~20% increase in peak oxygen uptake. In vivo cholinergic sensitivity and responsiveness were determined by dose‐response curves of acetylcholine (ACh) to sweat secretion rate on two forearm sites. ACh was administered via intradermal microdialysis while measuring cutaneous water loss (capacitance hygrometry) directly above the microdialysis membrane. Exercise training did not alter the number of cholinergic activated sweat glands or the dose‐response derived ED50 (2.0±0.1 to 2.1±0.1 ‐logM dose of ACh; P&gt;0.05). However, the maximal response to the highest dose of ACh was greater after exercise training (0.84±0.11 to 1.16±0.21 mg/cm2/min, P&lt;0.05). These data indicate that 8 weeks of aerobic exercise training does not increase in vivo cholinergic sensitivity as indicated by the ED50 but does increase maximal in vivo cholinergic responsiveness of human eccrine sweat glands.Support: HL77670, AG24420, M01 RR10732, C06 RR016499

Antigen expression of human eccrine sweat glands

The proliferating abilities of sweat glands are very limited, so researches on the repair and regeneration of sweat glands are important. First of all, we must find out reliable and specific antigen markers of sweat glands. To investigate the antigen expression of human eccrine sweat glands. The development of eccrine sweat glands was investigated by hematoxylin and eosin staining, and the antigen expression was detected by immunohistochemical techniques. Human eccrine sweat glands expressed cytokeratin (CK) 7, CK8, CK14, CK18, CK19 and epithelial membrane antigen (EMA). Carcinoembryonic antigen (CEA) was only expressed in sweat glands in the adult skin. Developing and developed sweat glands all had some cells expressing Ki67 and p63 antigens. Epidermal growth factor (EGF) was mainly localized in the secretory cells and ductal cells. Some myoepithelial cells were also labeled with anti-EGF antibody. In the older fetus, positive staining for EGF was seen in the lumen of the secretory portion. EGF receptor (EGFR) was expressed in the ducts. Human eccrine sweat glands express CK7, CK8, CK14, CK18, CK19, CEA, EMA, Ki67, p63, EGF and EGFR. In skin, CEA can be used as a specific immunological marker of sweat glands.

PAR-2 receptor-induced effects on human eccrine sweat gland cells

Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells

Background and aims Steroid hormones target K + channels as a means of regulating electrolyte and fluid transport. In this study, ion transporter targets of Estradiol (E2) were investigated in the human eccrine sweat gland cell line NCL-SG3. Results Whole cell patch-clamp studies revealed E2 (10 nM) rapidly activates a whole cell K + conductance, which is abolished by clotrimazole (30 μM), an inhibitor of the intermediate conductance calcium activated K + channel (IK Ca). The estrogen receptor (ER) antagonist ICI 182, 780 had no effect on this E2 activated K + conductance, suggesting an estrogen receptor independent mechanism of activation. Confocal microscopy studies revealed under basal conditions that the IK Ca channel is located within the cell cytoplasm and in the presence of E2, rapidly translocates to both the apical and basolateral membrane. In the presence of E2, tyrosine phosphorylation of calmodulin, which is known to regulate trafficking of the IK Ca channel, is increased, and treatment of cells with the calmodulin inhibitor trifluoperazine (TFP) prevents the E2-induced translocation. Conclusions Estradiol rapidly regulates a K + conductance through the IK Ca channel in an estrogen receptor independent manner. E2 stimulates the translocation of IK Ca to the cell membrane in a calmodulin dependent manner, representing a novel paradigm of estrogen action in sweat gland epithelial cells.

Na+ secretion rate increases proportionally more than the Na+ reabsorption rate with increases in sweat rate

The purpose of this study was to measure the in vivo Na(+) secretion and Na(+) reabsorption rates of the human eccrine sweat gland with increases in sweat rate. Such data should help to elucidate the physiological mechanism responsible for the previously reported linear relationship between increases in sweat rate and Na(+) concentration in sweat. On 5 days, each subject (n = 10) completed a 30-min exercise bout in an environmental chamber set at 35 degrees C and 40% relative humidity. The intensity for the five exercise bouts in the heat was set to approximate 50, 60, 70, 80, and 90% of age-predicted maximum heart rate. Forearm sweat samples and capillary blood samples were collected during each of the five 30-min exercise bouts. The sweat and blood samples were analyzed for Na(+) concentration in sweat and serum, which were used to calculate the rate of Na(+) secretion and Na(+) reabsorption. The mean correlation between sweat rate and Na(+) concentration in sweat was found to be r = 0.73. Within the sweat rate range of the present study, both Na(+) secretion rate and Na(+) reabsorption rate increased linearly; however, the Na(+) secretion rate increased almost twice as fast (slope = 141 vs. 80). Thus the rate at which Na(+) escaped reabsorption increased with increases in sweat rate and was significantly (P < 0.05) correlated to the Na(+) concentration in sweat (mean r = 0.90). Such results strongly suggest that the physiological mechanism responsible for the previously reported linear increase in Na(+) concentration in sweat seen with increases in sweat rate is that the Na(+) secretion rate increases proportionally more than the Na(+) reabsorption rate.

PAR‐2 receptor‐induced intracellular signalling in isolated intact human eccrine sweat gland cells and primary tissue culture cells

PAR‐2 receptors can evoke intracellular signalling and anion transport in a cell line derived from human sweat glands, however, it is unknown whether PAR‐2 receptors are present and play a role in intact human sweat gland secretory cells. PAR‐2 receptors were investigated in isolated sweat glands and tissue culture cells derived from primary explants. Skin samples were obtained by informed consent and ethics approval from volunteers for immunohistochemistry and sweat gland isolation for; Western blot analysis; calcium imaging or explanted for tissue culture. Immunohistochemistry and Western blot using an anti human PAR‐2 antibody demonstrated the presence of these receptors in sweat gland secretory cells. Calcium imaging experiments using trypsin and the agonist peptide SLIGKV showed that both could increase intracellular calcium levels in intact glands and in the primary sweat gland cultures. Results also demonstrated that the effects of the agonist peptide were reversible upon washout, but not trypsin, and that the reverse peptide VKGILS failed to initiate changes in intracellular calcium. The results of this study demonstrate that PAR‐2 receptors are present in isolated human sweat gland secretory cells and in primary cultured cells and that these receptors are functionally active and can induce increases in intracellular calcium.The study was supported by Glasgow Caledonian University.

17β-Estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC–PKA–Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3

We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate (200 microM) and the MEK inhibitor PD98059 (10 microM). We established E2 rapidly activates the novel PKC isoform PKCepsilon, PKA and Erk 1/2 MAPK in a PKCdelta and estrogen-receptor-dependent manner. The E2-induced effect was specific to 17beta-estradiol, as other steroids had no effect on [Ca2+]i. We have demonstrated a novel mechanism by which E2 rapidly modulates [Ca2+]i release from ryanodine-receptor-gated intracellular Ca2+ stores. The signal transduction pathway involves the estrogen receptor coupled to a PKC-PKA-Erk 1/2 signalling pathway.

Comparison of proliferating cells between human adult and fetal eccrine sweat glands

Studies of sweat glands had demonstrated that there were degenerating cells and proliferating cells in the eccrine sweat glands. To compare the differences in the proliferating cells between human adult and fetal eccrine sweat glands, immunostaining of proliferating-associated proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen (Ki67) was performed, and the location and the percentage of the positive staining cells were analyzed. The results showed that a few cells of the secretory and ductal portion in both the adult and fetal eccrine sweat glands stained positive with Ki67 and PCNA. The labeling index of PCNA in adult eccrine sweat glands was 34.71 +/- 8.37%, while that in the fetal was 62.72 +/- 6.54%. The labeling index of PCNA in fetal eccrine sweat glands was higher than that in adult. Myoepithelial cells were negative staining with anti-PCNA antibody in adult eccrine sweat glands, while in the fetal a few myoepithelial cells were positive staining. Labeling index of Ki67 in adult eccrine sweat glands was similar to that in the fetal, ranging from 0.5 to 4.3%. Myoepithelial cells of the adult and fetal eccrine sweat glands both were negative staining with anti-Ki67 antibody. We concluded that the myoepithelial cells had proliferating ability only in fetal eccrine sweat glands, and that the proliferating ability of fetal eccrine sweat glands was stronger than that of the adult.

Activation of chloride secretion via proteinase‐activated receptor 2 in a human eccrine sweat gland cell line – NCL‐SG3

Proteinase-activated receptor 2 (PAR-2) has been shown to elicit secretion in a variety of secretory epithelial cells by the transepithelial movement of chloride ions across the apical membrane. However, it is not known whether these receptors are present and/or functional in the secretory epithelial cells of the human eccrine sweat gland. To investigate this possibility mRNA analysis, Ca2+ microspectrofluorimetry and the short circuit current (Isc) technique were used to quantify electrolyte transport in a cell line (NCL-SG3) derived from human eccrine sweat gland secretory epithelia. The results provided molecular and functional evidence of the presence of PAR-2 receptors in the NCL-SG3 cells and show that these receptors can activate transepithelial Cl- secretion possibly via Ca2+-activated Cl- channels.

Sodium ion concentration vs. sweat rate relationship in humans

The purpose of this study was to determine the effect of active heat acclimation on the sweat osmolality and sweat sodium ion concentration vs. sweat rate relationship in humans. Eight healthy male volunteers completed 10 days of exercise in the heat. The mean exercising heart rate and core temperature were significantly decreased (P < 0.05) by 18 beats/min and 0.6 degrees C, respectively, following heat acclimation. Furthermore, sweat osmolality and the sweat sodium ion concentration vs. sweat rate relationships were shifted to the right. Specifically, the slopes of the relationships were not affected by heat acclimation. Rather, heat acclimation significantly reduced the y-intercepts of the sweat osmolality and sweat sodium relationships with sweat rate by 28 mosmol/kgH(2)O and 15 mmol/l, respectively. Thus there was a significantly lower sweat sodium ion concentration for a given sweat rate following heat acclimation. These results suggest that heat acclimation increases the sodium ion reabsorption capacity of the human eccrine sweat gland.

SIBLING Expression Patterns in Duct Epithelia Reflect the Degree of Metabolic Activity

The SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of secreted glycophosphoproteins includes bone sialoprotein (BSP), dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP), osteopontin (OPN), and matrix extracellular phosphoglycoprotein (MEPE). For many years, they were thought in normal adults to essentially be limited to metabolically active mesenchymal cells that assembled the mineralized matrices of bones and teeth. Over the last decade they have also been upregulated in a variety of tumors. Three of these proteins (BSP, OPN, and DMP1) have been shown to interact with three matrix metalloproteinases (MMP-2, MMP-3, and MMP-9, respectively). Recently, all five SIBLINGs and their MMP partners when known were observed in specific elements of normal ductal epithelia in salivary gland and kidney. We have hypothesized that the SIBLINGs and their MMP partners may be expressed in ductal cells with high metabolic activity. In this paper, we show that all the SIBLINGs (except MEPE) and their MMP partners are expressed in the metabolically active epithelia of human eccrine sweat gland duct but not in the more passive ductal cells of the macaque (monkey) lacrimal gland. It is hypothesized that MEPE expression may be limited to cells involved in active phosphate transport. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.