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Indian Journal of Dermatology,... 2022
Topics: Carcinoma, Skin Appendage; Demography; Humans; Mucins; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands
PubMed: 35593275
DOI: 10.25259/IJDVL_1260_20 -
Frontiers in Immunology 2022Cholinergic urticaria (CholU), a frequent form of chronic inducible urticaria, is characterized by itchy wheals and angioedema in response to sweating. As of now, the...
BACKGROUND
Cholinergic urticaria (CholU), a frequent form of chronic inducible urticaria, is characterized by itchy wheals and angioedema in response to sweating. As of now, the rate and pathophysiological relevance of impaired sweating in patients with CholU are ill-defined.
AIM
To assess in CholU patients the rate and extent of impaired sweating and its links to clinical and pathophysiological features of CholU.
PATIENTS AND METHODS
We assessed sweating in patients with CholU ( = 13) subjected to pulse-controlled ergometry (PCE) provocation testing. Pre- and post-PCE biopsies of lesional (L) and non-lesional (NL) skin were analyzed for the expression of acetylcholine receptor M3 (CHRM3) and acetylcholine esterase (ACh-E) by quantitative histomorphometry and compared to those of healthy control subjects (HCs). CholU patients were assessed for disease duration and severity as well as other clinical features.
RESULTS
Of the 13 patients with CholU, 10 showed reduced sweating in response to PCE provocation, and 3 had severely reduced sweating. Reduced sweating was linked to long disease duration and high disease severity. CholU patients with impaired sweating responses showed reduced sweat gland epithelial expression of CHRM3 and ACh-E.
CONCLUSION
Reduced sweating is common in CholU patients, especially in those with long-standing and severe disease, and it can be severe. Reduced expression of CHRM3 and ACh-E may be the cause or consequence of CholU in patients with impaired sweating, and this should be explored by further studies.
Topics: Acetylcholine; Acetylcholinesterase; Cholinergic Agents; Humans; Receptor, Muscarinic M3; Receptors, Cholinergic; Sweat Glands; Sweating; Urticaria
PubMed: 35967390
DOI: 10.3389/fimmu.2022.955161 -
Journal of the American Academy of... May 2022Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to...
Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin.
Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to identify clarifying immunohistochemical markers, molecular markers, or both. Clinicopathologic data (22 cases) were reviewed. Immunohistochemistry (insulinoma-associated protein 1, BCL-2, mucin 2 [MUC2], mucin 4, androgen receptor, β-catenin, and Merkel cell polyomavirus) and next-generation sequencing (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets, 468 genes) were performed (3 cases). Female patients (n = 15) and male patients (n = 7) (mean age 71.8 years; range 53-88 years) had eyelid or periorbital tumors (>90%) with mucin-containing solid or cystic neuroendocrine pathology. Immunohistochemistry (insulinoma-associated protein 1, BCL2, androgen receptor, retinoblastoma-associated protein 1, and β-catenin) was diffusely positive (5/5), MUC2 partial, mucin 4 focal, and Merkel cell polyomavirus negative. Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets identified 12 single-nucleotide variants and 1 in-frame deletion in 3 cases, each with DNA damage response or repair (BRD4, PPP4R2, and RTEL1) and tumor-suppressor pathway (BRD4, TP53, TSC1, and LATS2) mutations. Microsatellite instability, copy number alterations, and structural alterations were absent. Insulinoma-associated protein 1 and MUC2 are positive in endocrine mucin-producing sweat gland carcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNA damage repair and tumor-suppressor pathways may be implicated.
Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Skin Appendage; Cell Cycle Proteins; Female; High-Throughput Nucleotide Sequencing; Humans; Insulinoma; Male; Merkel cell polyomavirus; Middle Aged; Mucin-2; Mucin-4; Mucins; Mutation; Nuclear Proteins; Pancreatic Neoplasms; Protein Serine-Threonine Kinases; Receptors, Androgen; Repressor Proteins; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands; Transcription Factors; Tumor Suppressor Proteins; beta Catenin
PubMed: 33515627
DOI: 10.1016/j.jaad.2020.11.073 -
Journal of Dairy Science Nov 2022The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear...
The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear whether the mutation affects capacity for sweating. The objective of this observational study was to evaluate whether the SLICK1 mutation in PRLR alters characteristics of skin related to sweat gland abundance or function. Skin biopsies from 31 Holstein heifers, including 14 wild-type (SL) and 17 heterozygous slick (SL), were subjected to histological analysis to determine the percent of the surface area of skin sections that are occupied by sweat glands. We detected no effect of genotype on this variable. Immunohistochemical analysis of the forkhead transcription factor A1 (FOXA1), a protein essential for sweating in mice, from 6 SL and 6 SL heifers indicated twice as much FOXA1 in sweat glandular epithelia of SL heifers as in SL heifers. Results from RNA sequencing of skin biopsies from 5 SL and 7 SL heifers revealed few genes that were differentially expressed and none that have been associated with sweat gland development or function. In conclusion, results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, but do show that functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1, are modified by inheritance of the mutation in PRLR.
Topics: Animals; Cattle; Female; Mice; Forkhead Transcription Factors; Gene Expression; Mutation; Receptors, Prolactin; Sweat Glands
PubMed: 36085108
DOI: 10.3168/jds.2022-22272 -
Current Topics in Developmental Biology 2016The mammalian skin epidermis and its hair and sweat gland appendages provide a protective barrier that retains essential body fluids, guards against invasion by harmful... (Review)
Review
The mammalian skin epidermis and its hair and sweat gland appendages provide a protective barrier that retains essential body fluids, guards against invasion by harmful microbes, and regulates body temperature through the ability to sweat. At the interface between the external environment and the body, skin is constantly subjected to physical trauma and must also be primed to repair wounds in response to injury. In adults, the skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. This essay focuses on when stem cells become established during skin development and where these cells reside in adult epithelial tissues of the skin. I explore how skin stem cells maintain tissue homeostasis and repair wounds and how they regulate the delicate balance between proliferation and differentiation. Finally, I tackle the relation between skin cancer and mutations that perturb the regulation of stem cells.
Topics: Animals; Epidermal Cells; Epidermis; Epithelial Cells; Hair Follicle; Humans; Mammals; Skin; Skin Neoplasms; Stem Cells; Sweat Glands
PubMed: 26970628
DOI: 10.1016/bs.ctdb.2015.11.033 -
PloS One 2017Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even...
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.
Topics: Acetylcholine; Aquaporin 5; Biomarkers; Calcium Signaling; Cell Culture Techniques; Cell Polarity; Cell Survival; Cells, Cultured; Cholinergic Agonists; Humans; Models, Biological; Spheroids, Cellular; Sweat Glands; Transcriptome
PubMed: 28796813
DOI: 10.1371/journal.pone.0182752 -
Development (Cambridge, England) Oct 2014To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse...
To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse sweat gland formation. Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin - itself modulated by Dkk4 - with subsequent participation of Eda and Shh pathways.
Topics: Animals; DNA Primers; Ectodysplasins; Fluorescent Antibody Technique; Galactosides; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hedgehog Proteins; In Situ Hybridization; Indoles; Intercellular Signaling Peptides and Proteins; Mice; Mice, Transgenic; Real-Time Polymerase Chain Reaction; Sweat Glands; Wnt Proteins; Wnt Signaling Pathway; beta Catenin
PubMed: 25249463
DOI: 10.1242/dev.109231 -
Cell Cycle (Georgetown, Tex.) 2015The skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of...
The skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of perspiration. The aim of this study was to identify whether the key factors related to sweat gland development could directly reprogram fibroblasts into sweat gland-like cells. After introducing the NF-κB and Lef-1 genes into fibroblasts, we found that stably transfected fibroblasts expressed specific markers of sweat glands, including CEA, CK7, CK14 and CK19, both at the protein and mRNA levels. The immunofluorescence staining also showed positive expression of CEA, CK7, CK14 and CK19 in induced fibroblasts, but there were no positive cells in the control groups. The expression of Shh and Cyclin D1, downstream genes of NF-κB and Lef-1, were also significantly increased during regeneration. The induced fibroblasts were implanted into an animal model. Twenty days later, iodine-starch perspiration tests showed that 7 out of the 10 cell-treated paws were positive for perspiration, with a distinctive black point-like area appearing in the center of the paw. Contralateral paws tested negative. Histological examination of skin biopsies from experimental and control paws revealed that sweat glands were fully reconstructed in the test paws, with integral, secretory and ductal portions, but were not present in the control paws. This is the first report of successful reprogramming of fibroblasts into sweat gland-like cells, which will provide a new cell source for sweat gland regeneration in patients with extensive deep burns.
Topics: Animals; Carcinoembryonic Antigen; Cell Transdifferentiation; Cells, Cultured; Cellular Reprogramming; Cellular Reprogramming Techniques; Cyclin D1; Fibroblasts; Gene Expression Regulation, Developmental; Genetic Markers; Graft Survival; Hedgehog Proteins; Heterografts; Humans; Keratins; Lymphoid Enhancer-Binding Factor 1; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; Phenotype; RNA, Messenger; Sweat Glands; Sweating; Time Factors; Transfection
PubMed: 26566868
DOI: 10.1080/15384101.2015.1093707 -
Advanced Science (Weinheim,... Nov 2021Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate...
Restoration of sweat glands (SwGs) represents a great issue in patients with extensive skin defects. Recent methods combining organoid technology with cell fate reprogramming hold promise for developing new regenerative methods for SwG regeneration. Here, a practical strategy for engineering functional human SwGs in vitro and in vivo is provided. First, by forced expression of the ectodysplasin-A in human epidermal keratinocytes (HEKs) combined with specific SwG culture medium, HEKs are efficiently converted into SwG cells (iSwGCs). The iSwGCs show typical morphology, gene expression pattern, and functions resembling human primary SwG cells. Second, by culturing the iSwGCs in a special 3D culturing system, SwG organoids (iSwGOs) that exhibit structural and biological features characteristic of native SwGs are obtained. Finally, these iSwGOs are successfully transplanted into a mouse skin damage model and they develop into fully functioning SwGs in vivo. Regeneration of functional SwG organoids from reprogrammed HEKs highlights the great translational potential for personalized SwG regeneration in patients with large skin defects.
Topics: Adolescent; Adult; Animals; Disease Models, Animal; Epidermis; Female; Humans; Keratinocytes; Male; Mice; Mice, Nude; Organoids; Regeneration; Sweat Glands; Tissue Engineering; Wound Healing; Young Adult
PubMed: 34569165
DOI: 10.1002/advs.202103079 -
Annals of Surgery Jul 1956
Topics: Axilla; Humans; Lymph Nodes; Neoplasms; Sweat Gland Neoplasms; Sweat Glands
PubMed: 13327847
DOI: 10.1097/00000658-195607000-00015