Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 975
Filtrar
1.
J Dermatol ; 51(9): 1187-1198, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39087744

RESUMEN

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.


Asunto(s)
Acné Vulgar , Diana Mecanicista del Complejo 1 de la Rapamicina , Quinolonas , Glándulas Sebáceas , Sebo , Triglicéridos , Animales , Sebo/metabolismo , Sebo/efectos de los fármacos , Glándulas Sebáceas/efectos de los fármacos , Glándulas Sebáceas/patología , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/citología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Quinolonas/farmacología , Triglicéridos/metabolismo , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Aminopiridinas/farmacología , Diacilglicerol O-Acetiltransferasa/metabolismo , Diacilglicerol O-Acetiltransferasa/antagonistas & inhibidores , Cricetinae , Antibacterianos/farmacología , Perilipina-1/metabolismo , Estearoil-CoA Desaturasa/metabolismo , Estearoil-CoA Desaturasa/antagonistas & inhibidores , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Insulina/metabolismo , Mesocricetus
2.
Int Immunopharmacol ; 140: 112795, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39096873

RESUMEN

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT.


Asunto(s)
Acné Vulgar , Ácido Aminolevulínico , Mitocondrias , Estrés Oxidativo , Fotoquimioterapia , Propionibacterium acnes , Animales , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Acné Vulgar/tratamiento farmacológico , Fotoquimioterapia/métodos , Estrés Oxidativo/efectos de los fármacos , Propionibacterium acnes/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Línea Celular , Glándulas Sebáceas/efectos de los fármacos , Glándulas Sebáceas/patología , Glándulas Sebáceas/metabolismo , Humanos , Modelos Animales de Enfermedad , Metabolismo de los Lípidos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Oído/patología
3.
Arch Dermatol Res ; 316(7): 428, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904694

RESUMEN

Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat acne. We conducted experiments to quantitatively assess the effects of CBD on acne-related cellular pathways. SEB-1 sebocytes and HaCaT keratinocytes were exposed to various CBD concentrations. CBD exhibited a concentration-dependent impact on cell viability and notably reduced SEB-1 viability; furthermore, it induced apoptosis and a significant increase in the apoptotic area at higher concentrations. Additionally, CBD remarkably reduced pro-inflammatory cytokines, including CXCL8, IL-1α, and IL-1ß. Additionally, it inhibited lipid synthesis by modulating the AMPK-SREBP-1 pathway and effectively reduced hyperkeratinization-related protein keratin 16. Simultaneously, CBD stimulated the synthesis of elastin, collagen 1, and collagen 3. These findings emphasize the potential of CBD for the management of acne because of its anti-inflammatory, apoptotic, and lipid-inhibitory effects. Notably, the modulation of the Akt/AMPK-SREBP-1 pathway revealed a novel and promising mechanism that could address the pathogenesis of acne.


Asunto(s)
Acné Vulgar , Apoptosis , Cannabidiol , Supervivencia Celular , Queratinocitos , Transducción de Señal , Humanos , Acné Vulgar/tratamiento farmacológico , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Apoptosis/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Cicatriz/tratamiento farmacológico , Cicatriz/patología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Células HaCaT , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo III/metabolismo , Elastina/metabolismo , Glándulas Sebáceas/patología , Glándulas Sebáceas/efectos de los fármacos , Glándulas Sebáceas/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Línea Celular
4.
J Biol Chem ; 300(7): 107442, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38838779

RESUMEN

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.


Asunto(s)
Diferenciación Celular , Glándulas Sebáceas , Humanos , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/citología , Transcriptoma , Sebo/metabolismo , Transcripción Genética
5.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167195, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38648901

RESUMEN

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.


Asunto(s)
Acné Vulgar , Glándulas Sebáceas , Canales Catiónicos TRPV , Receptor Toll-Like 2 , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/genética , Animales , Acné Vulgar/metabolismo , Acné Vulgar/patología , Acné Vulgar/genética , Acné Vulgar/inmunología , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Humanos , Ratones , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/patología , Glándulas Sebáceas/inmunología , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Propionibacterium acnes , Masculino , FN-kappa B/metabolismo , Transducción de Señal , Ratones Endogámicos C57BL , Femenino
6.
BMC Genomics ; 25(1): 137, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310227

RESUMEN

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.


Asunto(s)
Glándulas Sebáceas , Piel , Humanos , Ratones , Animales , Glándulas Sebáceas/metabolismo , Piel/metabolismo , Perfilación de la Expresión Génica , Homeostasis , Aminoácidos/metabolismo
7.
Cells ; 13(4)2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38391942

RESUMEN

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.


Asunto(s)
Acné Vulgar , Lipogénesis , Humanos , Glándulas Sebáceas/metabolismo , Etanol/metabolismo , Adenosina Trifosfato/metabolismo
8.
J Allergy Clin Immunol ; 154(2): 480-491, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38157943

RESUMEN

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.


Asunto(s)
Citocinas , Interleucina-13 , Interleucina-4 , Glándulas Sebáceas , Sebo , Linfocitos T , Linfopoyetina del Estroma Tímico , Citocinas/metabolismo , Sebo/metabolismo , Sebo/inmunología , Interleucina-13/metabolismo , Interleucina-13/inmunología , Interleucina-4/metabolismo , Interleucina-4/inmunología , Animales , Glándulas Sebáceas/inmunología , Glándulas Sebáceas/metabolismo , Linfocitos T/inmunología , Humanos , Ratones , Tejido Adiposo/inmunología , Tejido Adiposo/metabolismo , Lipogénesis/inmunología , Ratones Endogámicos C57BL
9.
Sci Rep ; 13(1): 21576, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062074

RESUMEN

Emodin, a natural anthraquinone derivative, possesses anti-proliferative and anti-inflammatory properties in skin diseases. However, little information is available on the efficacy of emodin in treating acne vulgaris (acne). This study aims to investigate the protective effects and potential mechanisms of emodin as an anti-acne agent. In vitro, SZ95 sebocytes was chose to establish an acneigenic cellular model. We found that emodin effectively inhibited proliferation, induced cell cycle arrest and apoptosis of SZ95 sebocytes in a dose-dependent manner. To evaluate the lipid-lowering potential of emodin, we examined the levels of lipid contents and lipogenic transcription factors, and found that both lipid production and protein expression of PPARγ, LXR α/ß, and SREBP-1 were decreased after treatment with emodin. Furthermore, our results revealed that emodin inhibited sebaceous lipogenesis induced by insulin-like growth factor 1 (IGF-1), which was accompanied by a potent inhibition of the phosphoinositide-3-kinase (PI3K)/Akt/forkhead box protein O1 (FoxO1) pathway. In detail, emodin augmented the inhibitory effect of isotretinoin and PI3K inhibitor LY294002, while attenuating the activation of IGF-1 on PI3K/Akt/FoxO1 pathway. In addition, emodin could decrease the secretion of pro-inflammatory cytokines IL-6 and IL-8, and suppress the expression of NLRP3, capase-1, IL-1ß, and IL-18 in SZ95 sebocytes exposed to Cutibacterium acnes. Overall, our study provides preliminary evidence supporting the anti-growth, anti-lipogenic and anti-inflammatory properties of emodin, indicating the potential therapeutic application of emodin for acne treatment.


Asunto(s)
Acné Vulgar , Emodina , Humanos , Lipogénesis , Glándulas Sebáceas/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Emodina/farmacología , Emodina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Fosfatidilinositol 3-Quinasas/metabolismo , Acné Vulgar/microbiología , Proliferación Celular , Fosfatidilinositol 3-Quinasa/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Lípidos/farmacología
10.
Nutrients ; 15(15)2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37571253

RESUMEN

Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.


Asunto(s)
Ácido Linoleico , Ácido Palmítico , Ácido Palmítico/farmacología , Ácido Palmítico/metabolismo , Ácido Araquidónico/farmacología , Ácido Araquidónico/metabolismo , Ácido Linoleico/farmacología , Ácido Linoleico/metabolismo , Glándulas Sebáceas/metabolismo , Sebo , Lipogénesis
11.
Biotechnol J ; 18(11): e2300108, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37477791

RESUMEN

Acne is one of the most widespread skin diseases. The acne mechanism is intricate, involving interactions between different types of cells (i.e., sebocytes and macrophages). One of the challenges in studying the mechanism of acne is that current in vitro culture methods cannot reflect the 3D cellular environment in the tissue, including inflammatory stimuli and cellular interactions especially the interactions between sebocytes and immune cells. To solve this issue, we generated an in vitro acne disease model consisting of 3D artificial sebocyte glands and macrophages through the inertial focusing effect method. Using this model, we produced a controllable inflammatory environment similar to the acne pathogenetic process in the skin. The 3D artificial sebocyte glands and macrophages can be separated for analyzing each cell type, assisting the in-depth understanding of the acne mechanism. This study indicates that proinflammatory macrophages promote lipid accumulation and induce oxidative stress in sebocyte glands. Additionally, in an inflammatory environment, sebocyte glands induce macrophage polarization into the M1 phenotype. Employing this model for drug screening, we also demonstrated that, cannabidiol (CBD), a clinically investigated drug, is effective in restoring lipid accumulation, oxidative stress, inflammatory cytokines and macrophage polarization in the acne disease.


Asunto(s)
Acné Vulgar , Glándulas Sebáceas , Humanos , Glándulas Sebáceas/metabolismo , Acné Vulgar/metabolismo , Acné Vulgar/patología , Células Cultivadas , Células Epiteliales , Lípidos
12.
Cell Mol Biol Lett ; 28(1): 60, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37501148

RESUMEN

BACKGROUND: Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. METHODS: Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence. RESULTS: NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. CONCLUSIONS: Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.


Asunto(s)
Acné Vulgar , Glándulas Sebáceas , Animales , Femenino , Ratas , Acné Vulgar/metabolismo , Factores de Transcripción NFI/metabolismo , Ratas Sprague-Dawley , Glándulas Sebáceas/metabolismo , Sebo/metabolismo , Quinasas DyrK
13.
Exp Dermatol ; 32(10): 1717-1724, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37401827

RESUMEN

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.


Asunto(s)
Receptores ErbB , Rayos Infrarrojos , Enfermedades de las Glándulas Sebáceas , Glándulas Sebáceas , Animales , Cricetinae , Receptores ErbB/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedades de las Glándulas Sebáceas/etiología , Enfermedades de las Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Rayos Infrarrojos/efectos adversos
14.
Biochem Biophys Res Commun ; 667: 146-152, 2023 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-37229823

RESUMEN

BACKGROUND: Acne is associated with the excessive production of sebum, a complex mixture of lipids, in the sebaceous glands. The transcription factor Krüppel-like factor 4 (KLF4) plays an important role in skin morphogenesis, but its role in sebum production by sebocytes is not well known. PURPOSE: In this study, we investigated the possible action mechanism of KLF4 during calcium-induced lipogenesis in immortalized human sebocytes. METHODS: Sebocytes were treated with calcium, and lipid production was confirmed by thin-layer chromatography (TLC) and Oil Red O staining. To investigate the effect of KLF4, sebocytes were transduced with the KLF4-overexpressing adenovirus, and then lipid production was evaluated. RESULTS: Calcium treatment resulted in increased sebum production in terms of squalene synthesis in sebocytes. In addition, calcium increased the expression of lipogenic regulators such as sterol-regulatory element binding protein 1 (SREBP1), sterol-regulatory element binding protein 2 (SREBP2), and stearoyl-CoA desaturase (SCD). Similarly, the expression of KLF4 was increased by calcium in sebocytes. To investigate the effect of KLF4, we overexpressed KLF4 in sebocytes using recombinant adenovirus. As a result, KLF4 overexpression increased the expression of SREBP1, SREBP2, and SCD. Parallel to this result, lipid production was also increased by KLF4 overexpression. Chromatin immunoprecipitation revealed the binding of KLF4 to the SREBP1 promoter, indicating that KLF4 may directly regulate the expression of lipogenic regulators. CONCLUSION: These results suggest that KLF4 is a novel regulator of lipid production in sebocytes.


Asunto(s)
Calcio , Factor 4 Similar a Kruppel , Humanos , Calcio/metabolismo , Células Cultivadas , Lípidos , Lipogénesis , Glándulas Sebáceas/metabolismo , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , Esteroles/metabolismo
16.
Metabolomics ; 19(4): 21, 2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-36964290

RESUMEN

INTRODUCTION: Sebum-based metabolomics (a subset of "sebomics") is a developing field that involves the sampling, identification, and quantification of metabolites found in human sebum. Sebum is a lipid-rich oily substance secreted by the sebaceous glands onto the skin surface for skin homeostasis, lubrication, thermoregulation, and environmental protection. Interest in sebomics has grown over the last decade due to its potential for rapid analysis following non-invasive sampling for a range of clinical and environmental applications. OBJECTIVES: To provide an overview of various sebum sampling techniques with their associated challenges. To evaluate applications of sebum for clinical research, drug monitoring, and human biomonitoring. To provide a commentary of the opportunities of using sebum as a diagnostic biofluid in the future. METHODS: Bibliometric analyses of selected keywords regarding skin surface analysis using the Scopus search engine from 1960 to 2022 was performed on 12th January 2023. The published literature was compartmentalised based on what the work contributed to in the following areas: the understanding about sebum, its composition, the analytical technologies used, or the purpose of use of sebum. The findings were summarised in this review. RESULTS: Historically, about 15 methods of sampling have been used for sebum collection. The sample preparation approaches vary depending on the analytes of interest and are summarised. The use of sebum is not limited to just skin diseases or drug monitoring but also demonstrated for other systemic disease. Most of the work carried out for untargeted analysis of metabolites associated with sebum has been in the recent two decades. CONCLUSION: Sebum has a huge potential beyond skin research and understanding how one's physiological state affects or reflects on the skin metabolome via the sebaceous glands itself or by interactions with sebaceous secretion, will open doors for simpler biomonitoring. Sebum acts as a sink to environmental metabolites and has applications awaiting to be explored, such as biosecurity, cross-border migration, localised exposure to harmful substances, and high-throughput population screening. These applications will be possible with rapid advances in volatile headspace and lipidomics method development as well as the ability of the metabolomics community to annotate unknown species better. A key issue with skin surface analysis that remains unsolved is attributing the source of the metabolites found on the skin surface before meaningful biological interpretation.


Asunto(s)
Metabolómica , Sebo , Humanos , Glándulas Sebáceas/metabolismo
17.
Transl Vis Sci Technol ; 12(2): 4, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36735267

RESUMEN

Purpose: To identify the molecular background of eyelid sebaceous gland carcinomas (SCs), we conducted the integrated whole-exome sequencing and transcriptome sequencing for eyelid SCs in this study. Methods: The genetic alterations were studied by whole-exome sequencing, and the messenger RNA expression was studied using Oxford Nanopore Technologies (ONT) in five paired fresh eyelid SC tissues and adjacent normal tissues. Integrated analysis of exome and transcriptomic information was conducted for filtering candidate driver genes. Protein-protein interaction (PPI) network of filtered candidate genes was analyzed by STRING. The protein expression was verified by immunohistochemistry in 29 eyelid SCs and 17 compared normal sebaceous gland tissues. Results: The average numbers of pathogenic somatic single-nucleotide variants (SNVs) and indels in eyelid SCs were 75 and 28, respectively. Tumor protein p53 (TP53), zinc finger protein 750 (ZNF750), filaggrin 2 (FLG2), valosin-containing protein (VCP), and zinc finger protein 717 (ZNF717) were recurrent mutated genes. A mean of 844 differentially expressed genes (DEGs) were upregulated, and 1401 DEGs were downregulated in SC samples. The intersection of DEG-based pathways and mutation-based pathways was mainly involved in microbial infection and inflammation, immunodeficiency, cancer, lipid metabolism, and the other pathways. The intersection of DEGs and mutated genes consisted of 55 genes, of which 15 genes formed a PPI network with 4 clusters. The PPI cluster composed of scavenger receptor class B member 1 (SCARB1), peroxisome proliferator-activated receptor γ (PPARG), peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) was involved in cholesterol metabolism. The expression of SCARB1 protein was found to be increased, whereas that of PPARG protein was decreased in eyelid SCs compared to that in the normal sebaceous glands. Conclusions: Increased SCARB1 and decreased PPARG indicated that dysregulation of cholesterol metabolism might be involved in carcinogenesis of eyelid SCs. Translational Relevance: The malfunction in cholesterol metabolism might advance our knowledge of the carcinogenesis of eyelid SCs.


Asunto(s)
Carcinoma , Neoplasias de los Párpados , Humanos , Transcriptoma/genética , Exoma/genética , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/patología , PPAR gamma/genética , PPAR gamma/metabolismo , Secuenciación del Exoma , Neoplasias de los Párpados/genética , Neoplasias de los Párpados/metabolismo , Neoplasias de los Párpados/patología , Párpados , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Metabolismo de los Lípidos/genética , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Colesterol/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
18.
Exp Dermatol ; 32(6): 808-821, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36843338

RESUMEN

Sebum is a lipid-rich mixture secreted by the sebaceous gland (SG) onto the skin surface. By penetrating through the epidermis, sebum may be involved in the regulation of epidermal and dermal cells in both healthy and diseased skin conditions. Saturated and monounsaturated fatty acids (FAs), found as free FAs (FFAs) and in bound form in neutral lipids, are essential constituents of sebum and key players of the inflammatory processes occurring in the pilosebaceous unit in acne-prone skin. Little is known on the interplay among uptake of saturated FFAs, their biotransformation, and induction of proinflammatory cytokines in sebocytes. In the human SG, palmitate (C16:0) is the precursor of sapienate (C16:1n-10) formed by insertion of a double bond (DB) at the Δ6 position catalysed by the fatty acid desaturase 2 (FADS2) enzyme. Conversely, palmitoleate (C16:1n-7) is formed by insertion of a DB at the Δ9 position catalysed by the stearoyl coenzyme A desaturase 1 (SCD1) enzyme. Other FFAs processed in the SG, also undergo these main desaturation pathways. We investigated lipogenesis and release of IL-6 and IL-8 pro-inflammatory cytokines in SZ95 sebocytes in vitro after treatment with saturated FFAs, that is, C16:0, margarate (C17:0), and stearate (C18:0) with or without specific inhibitors of SCD1 and FADS2 desaturase enzymes, and a drug with mixed inhibitory effects on FADS1 and FADS2 activities. C16:0 underwent extended desaturation through both SCD1 and FADS2 catalysed pathways and displayed the strongest lipoinflammatory effects. Inhibition of desaturation pathways proved to enhance lipoinflammation induced by SFAs in SZ95 sebocytes. Palmitate (C16:0), margarate (C17:0), and stearate (C18:0) are saturated fatty acids that induce different arrays of neutral lipids (triglycerides) and dissimilar grades of inflammation in sebocytes.


Asunto(s)
Ácidos Grasos , Estearatos , Humanos , Ácidos Grasos/metabolismo , Estearatos/metabolismo , Glándulas Sebáceas/metabolismo , Citocinas/metabolismo , Palmitatos/metabolismo , Estearoil-CoA Desaturasa/metabolismo , Ácido Graso Desaturasas/metabolismo
19.
Mod Pathol ; 36(4): 100101, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36788082

RESUMEN

The accurate diagnosis of skin adnexal neoplasms is sometimes challenging but is necessary because medical management and follow-up may differ between tumors. GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin. We aimed to determine the diagnostic accuracy of GATA6 immunostaining to diagnose sebaceous tumors compared with that to diagnose other adnexal and nonadnexal cutaneous neoplasms. We conducted a retrospective, evaluator-nonblinded study comparing the reference standard (diagnosis by an expert dermatopathologist) with GATA6 immunostaining to identify sebaceous tumors in a cohort containing 234 different tumors. The GATA6 expression score was significatively higher in sebaceous than that in nonsebaceous tumors. In addition, tumors originating from the upper hair follicle showed positive results for GATA6 staining; however, they showed lower GATA6 expression scores. Detection of sebaceous tumors using GATA6 positivity had a sensitivity of 95.7% (95% CI, 85.8-99.2), specificity of 80.8% (95% CI, 74.5-85.8), positive predictive value of 55.6% (95% CI, 44.7-65.9), and negative predictive value of 98.7% (95% CI, 95.4-99.8). GATA6 showed similar sensitivity to adipophilin, the reference marker; however, the specificity of GATA6 was higher, as observed in a cohort of 106 tumors enriched in squamous cell carcinomas with clear-cell histology. In addition, GATA6 positivity was assessed in 39 sebaceous carcinomas and compared with epithelial membrane antigen (EMA), CK7, and androgen receptor (AR) staining results. Although CK7 staining displayed lower diagnostic performances, GATA6 staining showed comparable results as EMA and AR. Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.


Asunto(s)
Neoplasias de las Glándulas Sebáceas , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Neoplasias de las Glándulas Sebáceas/diagnóstico , Piel/patología , Neoplasias Cutáneas/patología , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/patología , Factor de Transcripción GATA6
20.
J Cosmet Dermatol ; 22(4): 1361-1368, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36700382

RESUMEN

BACKGROUND: The aim of this study was to explore the anti-inflammatory and anti-lipid effects of lactoferrin on SZ95 human sebaceous gland cells and mouse model of acne. METHODS: SZ95 cells were co-cultured with different concentrations of lactoferrin, and cell viability was determined using the 2,5-diphenyl-2H-tetrazolium bromide method. Oil red O and Nile red staining were performed to determine the lipid content. The mRNA expression of genes related to lipid metabolism (sterol regulatory element-binding protein-1 [SREBP-1], fatty acid synthase [FAS], stearoyl-CoA desaturase-1 [SCD-1], fatty acid desaturase 2 [FADS2]) and inflammation (interleukin-8 [IL-8]) was determined by reverse transcription-polymerase chain reaction. An acne mouse model was established using injection of P. acnes on the backs of mice. The proliferation and apoptosis of sebaceous gland cells were examined by immunohistochemistry against proliferating cell nuclear antigen (PCNA) and TUNEL staining, respectively. Western blotting was used to detect FADS2 and CXCL15 protein expression. RESULTS: Lactoferrin treatment at 10-500 µg/ml significantly decreased the lipid content, as revealed by the oil red O and Nile red staining. It also attenuated the increase of mRNA expression of SREBP-1, FAS, SCD-1, FADS2, and IL-8 in insulin-treated SZ95 cells. Moreover, lactoferrin treatment at the doses of 1-50 mg/mouse significantly reduced the inflammation and lipid production in the mouse model of acne. Also, the number of sebaceous gland cells was significantly reduced, and apoptosis was significantly increased by lactoferrin treatment in the mice. Mechanically, the levels of FADS2 and CXCL15 proteins in tissues were significantly decreased after lactoferrin treatment in the model mice. CONCLUSION: Our results demonstrate the potential of lactoferrin against sebogenesis, sebaceous gland inflammation in acne.


Asunto(s)
Acné Vulgar , Lactoferrina , Glándulas Sebáceas , Animales , Humanos , Ratones , Acné Vulgar/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-8/metabolismo , Lactoferrina/farmacología , Lipogénesis/fisiología , ARN Mensajero/metabolismo , Glándulas Sebáceas/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...