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1.
Mol Cell ; 70(4): 573-587.e4, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29775577

RESUMO

Apoptosis culminates in the activation of caspase-3, which plays an important role in implementing the cell death program. Here, we reveal a non-apoptotic role of caspase-3 as a key regulator of cell proliferation and organ size. Caspase-3 is specifically activated in the proliferating cells of the sebaceous gland, but does not instruct cell elimination. Deletion or chemical inhibition of caspase-3 diminishes cell proliferation, decreases cell number and reduces sebaceous gland size in vivo. Exploring the underlying mechanism, we demonstrate that α-catenin is cleaved by caspase-3, thus facilitating the activation and nuclear translocation of yes-associated protein (YAP), a vital regulator of organ size. Accordingly, activation of caspase-3 leads to YAP-dependent organ size augmentation. Finally, we show that X-linked inhibitor of apoptosis protein (XIAP) serves as an endogenous feedback antagonist for the caspase-3/YAP signaling module. Taken together, we report here a molecular mechanism wherein the apoptotic machinery is refocused to regulate cell proliferation and orchestrate organ size.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Caspase 3/fisiologia , Proliferação de Células , Retroalimentação Fisiológica , Proteínas Inibidoras de Apoptose/fisiologia , Fosfoproteínas/metabolismo , Fatores de Processamento de RNA/fisiologia , alfa Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Proteínas de Ciclo Celular , Feminino , Masculino , Camundongos , Camundongos Knockout , Tamanho do Órgão , Fosfoproteínas/genética , Transporte Proteico , Proteínas de Sinalização YAP , alfa Catenina/genética
2.
J Biol Chem ; 300(7): 107442, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838779

RESUMO

Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation via lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease.


Assuntos
Diferenciação Celular , Glândulas Sebáceas , Humanos , Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/citologia , Transcriptoma , Sebo/metabolismo , Transcrição Gênica
3.
J Allergy Clin Immunol ; 154(2): 480-491, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38157943

RESUMO

BACKGROUND: The cytokine TSLP promotes type 2 immune responses and can induce adipose loss by stimulating lipid loss from the skin through sebum secretion by sebaceous glands, which enhances the skin barrier. However, the mechanism by which TSLP upregulates sebaceous gland function is unknown. OBJECTIVES: This study investigated the mechanism by which TSLP stimulates sebum secretion and adipose loss. METHODS: RNA-sequencing analysis was performed on sebaceous glands isolated by laser capture microdissection and single-cell RNA-sequencing analysis was performed on sorted skin T cells. Sebocyte function was analyzed by histological analysis and sebum secretion in vivo and by measuring lipogenesis and proliferation in vitro. RESULTS: This study found that TSLP sequentially stimulated the expression of lipogenesis genes followed by cell death genes in sebaceous glands to induce holocrine secretion of sebum. TSLP did not affect sebaceous gland activity directly. Rather, single-cell RNA-sequencing revealed that TSLP recruited distinct T-cell clusters that produce IL-4 and IL-13, which were necessary for TSLP-induced adipose loss and sebum secretion. Moreover, IL-13 was sufficient to cause sebum secretion and adipose loss in vivo and to induce lipogenesis and proliferation of a human sebocyte cell line in vitro. CONCLUSIONS: This study proposes that TSLP stimulates T cells to deliver IL-4 and IL-13 to sebaceous glands, which enhances sebaceous gland function, turnover, and subsequent adipose loss.


Assuntos
Citocinas , Interleucina-13 , Interleucina-4 , Glândulas Sebáceas , Sebo , Linfócitos T , Linfopoietina do Estroma do Timo , Citocinas/metabolismo , Sebo/metabolismo , Sebo/imunologia , Interleucina-13/metabolismo , Interleucina-13/imunologia , Interleucina-4/metabolismo , Interleucina-4/imunologia , Animais , Glândulas Sebáceas/imunologia , Glândulas Sebáceas/metabolismo , Linfócitos T/imunologia , Humanos , Camundongos , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Lipogênese/imunologia , Camundongos Endogâmicos C57BL
4.
BMC Genomics ; 25(1): 137, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310227

RESUMO

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has been widely applied to dissect cellular heterogeneity in normal and diseased skin. Sebaceous glands, essential skin components with established functions in maintaining skin integrity and emerging roles in systemic energy metabolism, have been largely neglected in scRNA-seq studies. METHODS: Departing from mouse and human skin scRNA-seq datasets, we identified gene sets expressed especially in sebaceous glands with the open-source R-package oposSOM. RESULTS: The identified gene sets included sebaceous gland-typical genes as Scd3, Mgst1, Cidea, Awat2 and KRT7. Surprisingly, however, there was not a single overlap among the 100 highest, exclusively in sebaceous glands expressed transcripts in mouse and human samples. Notably, both species share a common core of only 25 transcripts, including mitochondrial and peroxisomal genes involved in fatty acid, amino acid, and glucose processing, thus highlighting the intense metabolic rate of this gland. CONCLUSIONS: This study highlights intrinsic differences in sebaceous lipid synthesis between mice and humans, and indicates an important role for peroxisomal processes in this context. Our data also provides attractive starting points for experimentally addressing novel candidates regulating sebaceous gland homeostasis.


Assuntos
Glândulas Sebáceas , Pele , Humanos , Camundongos , Animais , Glândulas Sebáceas/metabolismo , Pele/metabolismo , Perfilação da Expressão Gênica , Homeostase , Aminoácidos/metabolismo
5.
Mod Pathol ; 37(4): 100449, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369185

RESUMO

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.


Assuntos
Adenocarcinoma Sebáceo , Carcinoma de Células Escamosas , Neoplasias Oculares , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Sebáceas , Humanos , Prognóstico , Linfócitos do Interstício Tumoral/patologia , Carcinoma de Células Escamosas/patologia , Biomarcadores/metabolismo , Neoplasias Oculares/patologia , Neoplasias de Cabeça e Pescoço/patologia , Papillomavirus Humano
6.
Exp Dermatol ; 33(3): e15066, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38532571

RESUMO

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex-matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender-related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender.


Assuntos
Dermatite Atópica , Masculino , Adulto , Feminino , Humanos , Sebo , Glândulas Sebáceas , Pele , Lipídeos
7.
J Cutan Pathol ; 51(7): 513-517, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38613429

RESUMO

Seborrheic dermatitis is an inflammatory condition that usually presents with erythema, scaly greasy papules, and plaques affecting sebaceous gland-rich areas and predominantly involving the face and scalp. The diagnosis of seborrheic dermatitis can often be rendered based on the clinical presentation. However, in certain cases, a biopsy can be useful to distinguish it from clinical mimics such as psoriasis, discoid lupus, and rosacea. Prominent sebaceous gland atrophy without scarring has been well-described as an important and relatively specific clue for psoriatic or drug-induced alopecia. However, sebaceous gland atrophy is not specific to psoriasis and has been demonstrated in seborrheic dermatitis, facial discoid dermatitis, and potentially may occur in other inflammatory dermatoses of the scalp. We report a 23-year-old female patient presenting with non-scarring hair loss and histopathological findings demonstrating mild androgenetic alopecia and changes of seborrheic dermatitis with dramatic sebaceous gland atrophy. The patient had no history or evidence of psoriasis clinically. Our case suggests that in patients with seborrheic dermatitis, sebaceous gland atrophy may complicate the evaluation of alopecia biopsies and should be recognized as a pitfall. Seborrheic dermatitis should be included in the differential diagnosis of alopecia biopsies showing prominent sebaceous gland atrophy.


Assuntos
Alopecia , Atrofia , Dermatite Seborreica , Glândulas Sebáceas , Humanos , Feminino , Alopecia/patologia , Alopecia/diagnóstico , Dermatite Seborreica/patologia , Dermatite Seborreica/diagnóstico , Glândulas Sebáceas/patologia , Atrofia/patologia , Diagnóstico Diferencial , Adulto Jovem , Adulto
8.
Skin Res Technol ; 30(9): e70045, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39221850

RESUMO

BACKGROUND: Acne vulgaris poses a significant dermatological challenge, necessitating alternative treatments due to limitations and side effects associated with current therapies. This pilot clinical trial investigated the feasibility and efficacy of precision cryotherapy for acne vulgaris. METHODS: A total of 20 volunteers underwent targeted precision cryotherapy using a carbon dioxide-based device. Treatment outcomes were assessed using various parameters, including Investigator Global Assessment (IGA) score, acne lesion count, erythema index (EI), global evaluation score, and participant satisfaction. Safety monitoring included adverse event reporting and physical examination. RESULTS: Precision cryotherapy demonstrated a significant reduction (90.25%) in the acne lesion count by week 4, with clinical improvement indicated by IGA score reduction (p < 0.001). The EI showed notable improvements at weeks 1, 2, and 4. The global evaluation score demonstrated a 75%-100% clinical improvement at Visit 4. Participants reported high satisfaction (6.75 ± 0.79) with the procedure. No adverse event or discomfort was reported. CONCLUSION: Precision cryotherapy effectively improved acne lesions, which was safe and satisfactory for participants. These findings suggest its potential as an alternative therapeutic modality, especially for populations with limited treatment options. Further research is needed to validate the results and explore underlying mechanisms.


Assuntos
Acne Vulgar , Crioterapia , Satisfação do Paciente , Humanos , Acne Vulgar/terapia , Crioterapia/métodos , Feminino , Masculino , Adulto , Projetos Piloto , Adulto Jovem , Resultado do Tratamento , Adolescente , Estudos de Viabilidade
9.
Lasers Surg Med ; 56(2): 133-141, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38221810

RESUMO

BACKGROUND: Acne vulgaris (AV) is a prevalent skin condition known for its potential to cause scarring and psychological distress, often leading to diminished self-esteem. While topical and oral treatments are commonly prescribed, some patients experience treatment failure, adverse effects, or contraindications to conventional therapies. In response to these challenges, laser and energy-based device therapies have emerged as promising alternatives for individuals who fall into these categories, showing considerable potential in the treatment of AV. OBJECTIVE: This study aimed to evaluate the long-term efficacy and safety of a nonablative monopolar radiofrequency (NMRF) in treatment of moderate to severe AV. METHODS: Twenty-four patients with moderate to severe AV underwent a series of two NMRF treatment sessions, spaced 4 weeks apart. To evaluate treatment outcomes, live in-person lesion counts and measurements of pore size and volume, and sebum production were quantified using Antera® 3D imaging system, and Sebumeter®, respectively. Patients' self-assessment data regarding degree of improvement and facial oiliness were gathered. Dermatology life quality index (DLQI) questionnaire was utilized to assess the impact of AV on their quality of life. All objective and subjective evaluations were conducted at the baseline, 1 month after the first treatment, and during follow-up visits 1, 3, and 6 months after the last treatment sessions. Adverse effects were also recorded during each visit. RESULTS: Twenty out of the 24 subjects completed the study protocol. The mean inflammatory lesion counts significantly reduced by 42.86% and 45.71% from the baseline at 3 (p = 0.027) and 6 months (p = 0.032) after the second treatment. Sebum excretion likewise significantly decreased from baseline by 11.62% (p = 0.012), 13.37% (p < 0.001), and 21.51% (p = 0.004), 1 month after the first treatment, 1 and 6 months after the second treatment, respectively. The pore volume continued to decrease by 35% (p = 0.003) and 41.5% (p < 0.001) at 1 and 6 months following the final treatment, respectively. The DLQI significantly decreased from 10.00 (interquartile range [IQR]: 6.50-15.00) to 2.00 (IQR: 1.00-4.75), corresponding to 80% improvement of the index, 1 month after the last treatment and was sustained up to the last follow-up visit. Patients' self-assessments on degree of improvement and facial oiliness also significantly improved following NMRF treatments. The treatments were well-tolerated without significant adverse effects. CONCLUSION: NMRF appears to be an effective and safe treatment for inflammatory AV, with therapeutic outcomes persisting up to 6 months after two treatment sessions.


Assuntos
Acne Vulgar , Qualidade de Vida , Humanos , Acne Vulgar/terapia , Acne Vulgar/patologia , Resultado do Tratamento , Lasers , Falha de Tratamento
10.
Vet Dermatol ; 35(2): 238-241, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37968244

RESUMO

Finding an effective and well-tolerated treatment for canine idiopathic sebaceous adenitis (ISA) can be challenging. This case report describes an 8-year-old male Rottweiler with ISA successfully treated with a combination of oclacitinib and low doses of prednisolone.


Encontrar um tratamento eficaz e bem tolerado para a adenite sebácea idiopática (ISA) pode ser desafiador. Este relato descreve o caso de um cão Rottweiler macho de oito anos de idade tratado satisfatoriamente com uma associação de oclacitinib e baixas doses de prednisolona.


Encontrar un tratamiento efectivo y bien tolerado frente a la adenitis sebácea idiopática (ISA) puede ser un reto difícil. Este artículo describe el caso de un perro Rottweiler de ocho años tratado con eficacia con una combinación de oclacitinib y dosis bajas de prednisolona.


Trouver un traitement efficace et bien toléré pour l'adénite sébacée idiopathique canine (ASI) peut s'avérer difficile. Ce rapport clinique décrit le cas d'un Rottweiler mâle de 8 ans atteint d'ASI et traité avec succès par une combinaison d'oclacitinib et de faibles doses de prednisolone.


Assuntos
Dermatite , Doenças do Cão , Linfadenite , Masculino , Cães , Animais , Prednisolona/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Dermatite/tratamento farmacológico , Dermatite/veterinária , Doenças do Cão/tratamento farmacológico , Linfadenite/tratamento farmacológico , Linfadenite/veterinária
11.
J Dtsch Dermatol Ges ; 22(5): 730-747, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679790

RESUMO

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.


Assuntos
Neoplasias das Glândulas Sebáceas , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sebáceas/terapia , Neoplasias das Glândulas Sebáceas/diagnóstico , Humanos , Síndrome de Muir-Torre/patologia , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/terapia , Prognóstico , Adenocarcinoma Sebáceo/patologia , Adenocarcinoma Sebáceo/terapia , Adenocarcinoma Sebáceo/diagnóstico , Dermatologia/normas , Alemanha , Cirurgia de Mohs , Guias de Prática Clínica como Assunto
12.
Fetal Pediatr Pathol ; : 1-5, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39185734

RESUMO

Background: Caruncular sebaceous gland hyperplasia (SGH) is an uncommon, benign lesion. Its cause is still unclear. It has not been reported in the pediatric population, with few cases diagnosed in the fourth to eighth decades of life. Case Report: A 6-year-old boy presented with a slowly growing caruncular mass in the right eye. A diagnosis of caruncular SGH was made by histopathology. The clinical, histopathology, treatment, and prognosis are reviewed. Conclusion: This is the first described pediatric case of caruncular SGH that occurs since birth. There are many similarities between adult and pediatric caruncular SGH. Surgical excision is the recommended treatment.

13.
EMBO J ; 38(9)2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30886049

RESUMO

Mutations in Lef1 occur in human and mouse sebaceous gland (SG) tumors, but their contribution to carcinogenesis remains unclear. Since Gata6 controls lineage identity in SG, we investigated the link between these two transcription factors. Here, we show that Gata6 is a ß-catenin-independent transcriptional target of mutant Lef1. During epidermal development, Gata6 is expressed in a subset of Sox9-positive Lef1-negative hair follicle progenitors that give rise to the upper SG Overexpression of Gata6 by in utero lentiviral injection is sufficient to induce ectopic sebaceous gland elements. In mice overexpressing mutant Lef1, Gata6 ablation increases the total number of skin tumors yet decreases the proportion of SG tumors. The increased tumor burden correlates with impaired DNA mismatch repair and decreased expression of Mlh1 and Msh2 genes, defects frequently observed in human sebaceous neoplasia. Gata6 specifically marks human SG tumors and also defines tumors with elements of sebaceous differentiation, including a subset of basal cell carcinomas. Our findings reveal that Gata6 controls sebaceous gland development and cancer.


Assuntos
Fator de Transcrição GATA6/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/fisiologia , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias Cutâneas/patologia , Células-Tronco/patologia , Animais , Proliferação de Células , Dano ao DNA , Feminino , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/genética , Masculino , Camundongos , Camundongos Knockout , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Mutação , Neoplasias das Glândulas Sebáceas/genética , Neoplasias das Glândulas Sebáceas/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Células-Tronco/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
14.
Exp Dermatol ; 32(1): 78-84, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36114818

RESUMO

Lipids synthesized on the skin are critical to the antimicrobial barrier. Skin lipids also facilitate survival of lipophilic skin commensals in an otherwise dry and acidic ecological landscape. Thus, skin-specific stearoyl-coenzyme A desaturase 1 knockout mice (Scd1ΔK14 ) with sebocyte atrophy and decreased synthesis of monounsaturated fatty acids, triglycerides and wax diesters have dry, inflamed skin. Here, we used 16S rRNA (V1-V2 and V1-V9) and internal transcribed spacer 1 (ITS1) amplicon sequencing to compare bacterial and fungal skin microbiomes between Scd1ΔK14 mice and wildtype control mice (Scd1fl/fl ) in a barrier facility. Saprophytic bacteria including Sporosarcina spp. and Staphylococcus lentus and saprophytic fungi including Alternaria infectoria were found in higher relative abundance in the Scd1ΔK14 group (ANCOM). Analysis of community diversity (Shannon index) revealed greater fungal alpha diversity in the Scd1ΔK14 group (p = 0.009, Kruskal-Wallis). Principal coordinates analysis (Bray-Curtis dissimilarity) showed that both bacterial (p = 0.002, PERMANOVA) and fungal communities (p = 0.006, PERMANOVA) of the Scd1ΔK14 group were unique from the wildtype group. Altogether, these results suggest that sebaceous gland-derived lipids normally restrict the skin microbiome, and in the absence of these lipids, a greater diversity of opportunistic organisms are able to colonize the surface of skin.


Assuntos
Pele , Estearoil-CoA Dessaturase , Animais , Camundongos , Acil Coenzima A , Camundongos Knockout , RNA Ribossômico 16S/genética , Estearoil-CoA Dessaturase/genética , Triglicerídeos
15.
Exp Dermatol ; 32(7): 1120-1131, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37088961

RESUMO

Recent data indicate that distinct skin areas show different microbial/chemical milieu. Keratinocytes (KC) respond to these stimuli by producing cytokine mediators. Therefore, we aimed to determine KC-derived cytokine expression in distinct healthy skin regions (gland-poor [GP], sebaceous gland-rich [SGR] and apocrine gland-rich [AGR]), and their changes in skin diseases of the given regions (atopic dermatitis [AD], papulopustular rosacea [PPR] and psoriasis). Cytokines were analysed at the mRNA and protein levels, and literature analysis was performed for functional categorization. The three regions showed characteristically different cytokine patterns. GP was featured by an IL-25/IL-33/IL-36RA/IL-38/IL-18 cytokine milieu, SGR was characterized by IL-23/IL-17C/IL-18, and AGR skin exhibited a mixed IL-25/IL-33/IL-23/IL-18 profile. Literature analyses revealed different homeostatic and proinflammatory roles of these cytokine patterns (Th2 related in GP, Th17 related in SGR and mixed Th2/Th17 in AGR). In skin diseases which are primarily epidermal cytokine-driven (AD, PPR), the level of the regionally characteristic cytokines were further elevated, in contrast to the autoantigen-driven psoriasis, where the cytokine pattern was independent from the localization. Healthy skin regions are equipped with different KC-derived cytokine profiles, which may influence each region's capability of mediator production in certain types of dermatoses.


Assuntos
Dermatite Atópica , Psoríase , Rosácea , Humanos , Interleucina-18/metabolismo , Interleucina-33/metabolismo , Epiderme/metabolismo , Queratinócitos/metabolismo , Psoríase/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Dermatite Atópica/metabolismo , Rosácea/metabolismo , Interleucina-23/metabolismo , Interleucinas/metabolismo
16.
Exp Dermatol ; 32(10): 1717-1724, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37401827

RESUMO

As near-infrared radiation (NIR), which is a composition of sunlight with an 780-1400 nm wavelength, is associated with skin aging such as wrinkles and slacks, the biological actions of NIR with high dermal penetration remains unclear. In the present study, we found that NIR irradiation (40 J/cm2 ) at different levels of irradiance (95-190 mW/cm2 ) using a laboratory device with a xenon flash lamp (780-1700 nm) caused sebaceous gland enlargement concomitantly with skin thickening in the auricle skin of hamsters. The sebaceous gland enlargement resulted from the proliferation of sebocytes due to an increase in the number of proliferating cell nuclear antigen (PCNA)- and lamin B1-positive cells in vivo. In addition, NIR irradiation transcriptionally augmented the production of epidermal growth factor receptor (EGFR) accompanied with an increase in the reactive oxygen species (ROS) level in hamster sebocytes in vitro. Furthermore, the administration of hydrogen peroxide increased the level of EGFR mRNA in the sebocytes. Therefore, these results provide novel evidence that NIR irradiation causes the hyperplasia of sebaceous glands in hamsters by mechanisms in which EGFR production is transcriptionally augmented through ROS-dependent pathways in sebocytes.


Assuntos
Receptores ErbB , Raios Infravermelhos , Doenças das Glândulas Sebáceas , Glândulas Sebáceas , Animais , Cricetinae , Receptores ErbB/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças das Glândulas Sebáceas/etiologia , Doenças das Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Raios Infravermelhos/efeitos adversos
17.
Bioessays ; 43(10): e2100126, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34486148

RESUMO

MPZL3 is a nuclear-encoded, mitochondrially localized, immunoglobulin-like V-type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology.


Assuntos
Folículo Piloso , Mitocôndrias , Animais , Proteínas CLOCK , Diferenciação Celular , Ritmo Circadiano , Proteínas de Membrana , Camundongos , Camundongos Knockout , Mitocôndrias/genética
18.
BMC Ophthalmol ; 23(1): 390, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752463

RESUMO

BACKGROUND: Human papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across studies. This study aimed to investigate the presence of HPV in eyelid SGC and SCC among Koreans and its correlation with clinicopathological characteristics. METHODS: Surgically resected eyelid samples diagnosed as SGC or SCC from January 1999 to June 2011 were identified from the pathology database of three referral centres in Korea. Clinicopathological information including origin (skin vs. tarsal conjunctiva) and treatment outcomes were retrospectively reviewed. Immunohistochemistry (IHC) for p16, HPV DNA in situ hybridisation (ISH), and polymerase chain reaction-based DNA microarray were performed in paraffin-embedded tissue sections. RESULTS: Our cohort included 34 SGC and 12 SCC cases with Asian ethnicity. HPV was detected in 4 SGC and 6 SCC by DNA microarray, while 2 SCC (16.7%) showed positivity in ISH. SCC of tarsal conjunctival origin was significantly more common in HPV-positive SCC than in HPV-negative SCC (5 of 6 vs. 0 of 6, P = 0.015, Fisher's exact test). Among samples showing positive staining in p16 IHC, HPV positivity rates were 0.0% (0/19) in SGC and 100% (3/3) in SCC. There was no significant difference in overall and local recurrence rate in eyelid SGC and SCC according to the HPV status (P > 0.99). CONCLUSIONS: HPV was found in a subset of eyelid SGC and SCC among Koreans and might be aetiologically related to SCC of tarsal conjunctival origin. Overexpression of p16 is considered to be inappropriate as an indicator of HPV infection in eyelid SGC. Further investigation is required to elucidate the transmission route and pathogenic roles of HPV.


Assuntos
Adenocarcinoma Sebáceo , Carcinoma , Neoplasias Palpebrais , Infecções por Papillomavirus , Neoplasias das Glândulas Sebáceas , Neoplasias Cutâneas , Humanos , Neoplasias Palpebrais/epidemiologia , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Prevalência , População do Leste Asiático , Estudos Retrospectivos
19.
Australas J Dermatol ; 64(4): 529-533, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37461361

RESUMO

Sebaceous carcinoma is a rare cutaneous malignancy which is typically regarded as relatively aggressive and has traditionally been subdivided into periorbital or extraorbital tumours. We conducted a retrospective review of all cases of sebaceous carcinoma reported to the Western Australian Cancer Registry between 1987 and May 2019. The incidence of sebaceous carcinoma in Western Australia has increased over the last three decades, with extraorbital tumours being much more common than periorbital tumours. Very few sebaceous carcinomas have led directly to the death of patients; however, adverse outcomes were more likely with periorbital tumours, in particular local recurrence and the need for major surgical intervention.


Assuntos
Adenocarcinoma Sebáceo , Neoplasias das Glândulas Sebáceas , Humanos , Austrália Ocidental/epidemiologia , Austrália/epidemiologia , Adenocarcinoma Sebáceo/epidemiologia , Neoplasias das Glândulas Sebáceas/patologia , Sistema de Registros
20.
Int J Mol Sci ; 24(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37373478

RESUMO

The seeds of Moringa oleifera (horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal-Wallis test and Dunn's multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.


Assuntos
Moringa oleifera , Moringa , Humanos , Moringa oleifera/química , Azeite de Oliva/farmacologia , Azeite de Oliva/análise , Sementes/química , Ácidos Graxos/análise , Óleos de Plantas/química , Ácido Oleico/farmacologia , Ácido Oleico/análise , Citocinas/análise
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