Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Exp Dermatol ; 33(3): e15066, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38532571

RESUMEN

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.


Asunto(s)
Dermatitis Atópica , Masculino , Adulto , Femenino , Humanos , Sebo , Glándulas Sebáceas , Piel , Lípidos
2.
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
3.
Development ; 143(10): 1823-31, 2016 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-26989175

RESUMEN

Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras(G12D) mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.


Asunto(s)
Apoptosis/efectos de la radiación , Ojo/efectos de la radiación , Lípidos/química , Glándulas Sebáceas/química , Rayos Ultravioleta , Agua/química , Animales , Regulación de la Temperatura Corporal/efectos de la radiación , Síndromes de Ojo Seco/complicaciones , Síndromes de Ojo Seco/patología , Homocigoto , Humanos , Inflamación/complicaciones , Inflamación/patología , Integrasas/metabolismo , Glándulas Tarsales/metabolismo , Glándulas Tarsales/efectos de la radiación , Ratones Endogámicos C57BL , Tamaño de los Órganos , Especificidad de Órganos/efectos de la radiación , Fenotipo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Sebo/metabolismo
4.
J Lipid Res ; 57(6): 1051-8, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27127078

RESUMEN

Acne is a multifactorial skin disorder frequently observed during adolescence with different grades of severity. Multiple factors centering on sebum secretion are implicated in acne pathogenesis. Despite the recognized role of sebum, its compositional complexity and limited analytical approaches have hampered investigation of alterations specifically associated with acne. To examine the profiles of lipid distribution in acne sebum, 61 adolescents (29 males and 32 females) were enrolled in this study. Seventeen subjects presented no apparent clinical signs of acne. The 44 affected individuals were clinically classified as mild (13 individuals), moderate (19 individuals), and severe (12 individuals) acne. Sebum was sampled from the forehead with Sebutape(TM) adhesive patches. Profiles of neutral lipids were acquired with rapid-resolution reversed-phase/HPLC-TOF/MS in positive ion mode. Univariate and multivariate statistical analyses led to the identification of lipid species with significantly different levels between healthy and acne sebum. The majority of differentiating lipid species were diacylglycerols (DGs), followed by fatty acyls, sterols, and prenols. Overall, the data indicated an association between the clinical grading of acne and sebaceous lipid fingerprints and highlighted DGs as more abundant in sebum from adolescents affected with acne.


Asunto(s)
Acné Vulgar/metabolismo , Diglicéridos/aislamiento & purificación , Lípidos/aislamiento & purificación , Piel/metabolismo , Esteroles/aislamiento & purificación , Acné Vulgar/patología , Adolescente , Adulto , Cromatografía Líquida de Alta Presión , Diglicéridos/metabolismo , Femenino , Hemiterpenos , Humanos , Lípidos/química , Lípidos/clasificación , Masculino , Pentanoles/química , Pentanoles/aislamiento & purificación , Sebo/metabolismo , Índice de Severidad de la Enfermedad , Piel/química , Piel/patología , Esteroles/metabolismo
5.
Exp Dermatol ; 24(4): 245-51, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25644500

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.


Asunto(s)
PPAR gamma/fisiología , Fenómenos Fisiológicos de la Piel , Animales , Cabello/fisiología , Enfermedades del Cabello/etiología , Enfermedades del Cabello/fisiopatología , Humanos , Mediadores de Inflamación/fisiología , Ligandos , PPAR gamma/agonistas , Transducción de Señal , Piel/efectos de los fármacos , Piel/patología , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/fisiología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/fisiopatología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/prevención & control , Tiazolidinedionas/farmacología
6.
Biochim Biophys Acta ; 1830(10): 4642-9, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23688400

RESUMEN

BACKGROUND: Lipid synthesis and storage are accomplished by lipid droplets (LDs). The perilipin family of LD-associated proteins, comprising 5 members (PLIN1-PLIN5), has been well characterized in adipocytes but not in sebocytes, epithelial cells in which LD formation is a key feature of the cellular differentiation. METHODS: Perilipin expression in the sebaceous gland cell line SZ95 and in human sebaceous glands was studied by qRT-PCR, Western blots, and immunohistochemistry. Lipid accumulation was evaluated by Nile red staining and mass spectrometry. RESULTS: PLIN2 and PLIN3 are the most abundant perilipins in undifferentiated sebocytes. Induction of lipogenesis by linoleic acid (LA) resulted in increased transcript levels of all perilipins except for PLIN3 and in a time-dependent increase of PLIN2 protein. Nile red staining revealed that siRNA-mediated downregulation of PLIN2 significantly impaired basal and LA-induced lipid accumulation. Mass spectrometry revealed PLIN2 deficiency to cause a reduction in the amount of several specific lipid fractions, including di- and triacyl-glycerol esters, phosphatidylcholine lipids, and ceramides in sebocytes under basal conditions. In contrast, PLIN2 downregulation exerted a statistically significant inhibitory effect only on the accumulation of specific LA-induced triglycerides. PLIN2-deficient mice showed normal morphology of sebaceous glands. However, their sebaceous glands were significantly reduced in size and showed less cell proliferation. CONCLUSIONS: PLIN2 is the major perilipin regulated during sebocyte differentiation in vitro. PLIN2 is also important for sebaceous lipid accumulation in vitro and regulates sebaceous gland size in vivo. GENERAL SIGNIFICANCE: Our study provides the first systematic analysis of LD-associated proteins in sebocytes.


Asunto(s)
Diferenciación Celular , Metabolismo de los Lípidos , Proteínas de la Membrana/fisiología , Glándulas Sebáceas/citología , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Humanos , Proteínas de la Membrana/metabolismo , Ratones , Perilipina-2 , Reacción en Cadena de la Polimerasa , Glándulas Sebáceas/metabolismo
7.
Exp Dermatol ; 23(10): 759-61, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25039349

RESUMEN

Lipid droplets (LD) are dynamic organelles that manage cellular lipid synthesis, storage and retrieval. Although LD-associated proteins, including the perilipin family (PLIN1-PLIN5), are essential for these functions, they have been poorly characterized in sebocytes. Here, we employed siRNAs to downregulate PLIN3 in SZ95 sebaceous gland cells and evaluated the consequences in lipid accumulation by nile red staining and mass spectrometry. Nile red staining revealed that siRNA-mediated downregulation of PLIN3 significantly impaired linoleic acid-induced lipid accumulation in SZ95 sebocytes. Mass spectrometry revealed that PLIN3 was implicated in the metabolism of linoleic acid, a lipid source used in the build-up of triglycerides, among other acyl lipids. Furthermore, the expression of key enzymes of sebaceous lipogenesis was altered in PLIN3-deficient sebocytes, consistent with the changes observed in the neutral lipid abundance, suggesting that PLIN3 functions are intertwined with the lipogenic pathways implicated in sebaceous lipogenesis, such as desaturation and triglyceride synthesis.


Asunto(s)
Lipogénesis , Glándulas Sebáceas/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Línea Celular , Regulación hacia Abajo , Humanos , Ácido Linoleico/metabolismo , Lipogénesis/genética , Redes y Vías Metabólicas , Perilipina-3 , ARN Interferente Pequeño/genética , Glándulas Sebáceas/citología , Triglicéridos/metabolismo , Proteínas de Transporte Vesicular/antagonistas & inhibidores , Proteínas de Transporte Vesicular/genética
8.
Sci Rep ; 14(1): 40, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167931

RESUMEN

Lipids are key constituents of the barrier function in the human stratum corneum (SC), which is the outermost layer of the epidermis and amenable to non-invasive sampling by tape stripping. The three major lipid classes in the SC, i.e., ceramides, fatty acids, and cholesterol, present equimolar concentration. Liquid chromatography coupled with mass spectrometry (LCMS) is elective in profiling lipids in the SC in both positive and negative ion modes. Nevertheless, the latter one allows for the simultaneous detection of the three major epidermal components of the SC. Determination of ceramides in the SC poses analytical challenges due to their wide range of structures and concentrations especially in the case of limited sample amounts. Ammonium formate is a commonly used modifier added to the mobile phase to assist ionization. However, it introduces uncertainty in the identification of ceramides when operating in negative ion mode, even with high resolution MS. We tested the advantages of using fluoride in the lipid profiling of SC and unambiguous identification of ceramides subclasses. The use of fluoride enhanced the ionization of ceramides, regardless the specific substructure, solved misidentification issues, and was successfully applied to the simultaneous detection of all three lipid classes in the human SC.


Asunto(s)
Fluoruros , Compuestos de Flúor , Humanos , Fluoruros/análisis , Cromatografía de Fase Inversa , Epidermis/química , Espectrometría de Masas/métodos , Ceramidas/análisis
9.
Biomed Pharmacother ; 175: 116662, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692064

RESUMEN

17-ß-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-ß-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-ß-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-ß-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-ß-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-ß-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-ß-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-ß-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-ß-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17ß-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17ß-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-ß-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.


Asunto(s)
Androstenodiona , Amianto , Biomarcadores de Tumor , Estradiol , Neoplasias Pulmonares , Mesotelioma Maligno , Exposición Profesional , Humanos , Estradiol/sangre , Masculino , Biomarcadores de Tumor/sangre , Androstenodiona/sangre , Amianto/toxicidad , Amianto/efectos adversos , Femenino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Anciano , Mesotelioma Maligno/sangre , Mesotelioma Maligno/diagnóstico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Mesotelioma/sangre , Mesotelioma/diagnóstico , Mesotelioma/inducido químicamente , Neoplasias Pleurales/sangre , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/inducido químicamente , Deshidroepiandrosterona/sangre , Estudios de Casos y Controles , Detección Precoz del Cáncer/métodos
10.
Cells ; 13(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38727296

RESUMEN

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism.


Asunto(s)
Citocinas , Quinasas Janus , Metabolismo de los Lípidos , Factores de Transcripción STAT , Células Th2 , Humanos , Citocinas/metabolismo , Epidermis/metabolismo , Epidermis/efectos de los fármacos , Ácidos Grasos/metabolismo , Interleucina-4/metabolismo , Inhibidores de las Cinasas Janus/farmacología , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Piperidinas/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Factores de Transcripción STAT/antagonistas & inhibidores , Factores de Transcripción STAT/metabolismo , Células Th2/metabolismo , Células Th2/efectos de los fármacos , Técnicas de Cultivo Tridimensional de Células
11.
Biofilm ; 8: 100222, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39381779

RESUMEN

Atopic dermatitis (AD) is a chronic inflammatory skin disorder exacerbated by Staphylococcus aureus colonization. The specific factors that drive S. aureus overgrowth and persistence in AD remain poorly understood. This study analyzed skin barrier functions and microbiome diversity in lesional (LE) and non-lesional (NL) forearm sites of individuals with severe AD compared to healthy control subjects (HS). Notable differences were found in transepidermal water loss, stratum corneum hydration, and microbiome composition. Cutibacterium was more prevalent in HS, while S. aureus and S. lugdunensis were predominantly found in AD LE skin. The results highlighted that microbial balance depends on inter-species competition. Specifically, network analysis at the genus level demonstrated that overall bacterial correlations were higher in HS, indicating a more stable microbial community. Notably, network analysis at the species level revealed that S. aureus engaged in competitive interactions in NL and LE but not in HS. Whole-genome sequencing (WGS) showed considerable genetic diversity among S. aureus strains from AD. Despite this variability, the isolates exhibited convergence in key phenotypic traits such as adhesion and biofilm formation, which are crucial for microbial persistence. These common phenotypes suggest an adaptive evolution, driven by competition in the AD skin microenvironment, of S. aureus and underscoring the interplay between genetic diversity and phenotypic convergence in microbial adaptation.

12.
Exp Dermatol ; 22(1): 41-7, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23278893

RESUMEN

Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long-time treatment with AzA. We previously unrevealed that anti-inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo-aggravated disease, we investigated the ability of AzA to counteract stress-induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8-methoxypsoralen (PUVA), previously reported to activate a senescence-like phenotype, including long-term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence-associated ß-galactosidase (SA-ß-gal). We found that PUVA-treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP-1 release and SA-ß-galactosidase-positive cells. Moreover, AzA induced a reduction in ROS generation, an up-modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA-treated HDFs. Further evidences of AzA anti-senescence effect were repression of p53 and p21, increase in type I pro-collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA-SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA-induced senescence-like phenotype and its ability to activate PPAR-γ provides relevant insights into the anti-senescence mechanism.


Asunto(s)
Senescencia Celular/efectos de los fármacos , Fármacos Dermatológicos/farmacología , Ácidos Dicarboxílicos/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , PPAR gamma/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Senescencia Celular/efectos de la radiación , Colágeno Tipo I/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Fibroblastos/citología , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Metaloproteinasa 1 de la Matriz/metabolismo , Metoxaleno/farmacología , Terapia PUVA , Fenotipo , Fosfolípidos/metabolismo , Fármacos Fotosensibilizantes/farmacología , Procolágeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Células Madre/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Rayos Ultravioleta , beta-Galactosidasa/metabolismo
13.
Front Physiol ; 14: 1252972, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37727660

RESUMEN

Insulin affects metabolic processes in different organs, including the skin. The sebaceous gland (SG) is an important appendage in the skin, which responds to insulin-mediated signals, either directly or through the insulin growth factor 1 (IGF-1) axis. Insulin cues are differently translated into the activation of metabolic processes depending on several factors, including glucose levels, receptor sensitivity, and sebocyte differentiation. The effects of diet on both the physiological function and pathological conditions of the SG have been linked to pathways activated by insulin and IGF-1. Experimental evidence and theoretical speculations support the association of insulin resistance with acne vulgaris, which is a major disorder of the SG. In this review, we examined the effects of insulin on the SG function and their implications in the pathogenesis of acne.

14.
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
15.
Front Mol Biosci ; 10: 1176802, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37363400

RESUMEN

Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulfate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI's cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.

16.
Sci Rep ; 11(1): 16591, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-34400712

RESUMEN

Lipidomics is advantageous in the study of sebum perturbations occurring in acne. An extended evaluation of the sebum lipid profiles in acne-prone sebaceous areas is lacking in dark skin. Yet, there is a void space in understanding how the building blocks of sebum lipids, i.e. individual fatty acids (FAs), are intertwined with acne-prone skin. We aimed to determine the sebum lipidome in facial areas of adolescents with and without acne in Nigeria. A cross-sectional analytical study was conducted in 60 adolescents/young adults divided in 30 acne patients (15F, 15M) and 30 age and sex-matched controls. Sebum samples obtained from foreheads and cheeks were analysed separately by gas chromatography-mass spectrometry (GCMS) and thin layer chromatography (HPTLC). Distributions of sebum components were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). Sebum incretion in acne was paralleled by significantly higher abundance of triglycerides, wax esters, and squalene together with monounsaturated FAs (MUFAs), and straight chain saturated FAs (SFAs), especially those with odd-carbon chain, i.e. C13:0, C15:0, and C17:0. Profiling weight/weight percentage of individual components revealed that, in acne, the free FAs (FFAs) array was shifted towards higher relative abundance of the SFAs C15:0, C16:0, and C17:0 and lower percentage of the anteiso-branched FFAs with 12, 14, 16, and 18 carbons. In acne patients, MUFAs and PUFAs were quantitatively increased and decreased on foreheads and cheeks, respectively. Relative abundance of fatty alcohols was decreased in acne independent on the site. The results indicated that acne associates with site-specific derangement of the pathways regulating the balance among odd straight-chain and branched-chain SFAs, MUFAs, which included sapienate (C16:1n-10), PUFAs, and squalene.


Asunto(s)
Acné Vulgar/metabolismo , Cara , Lipidómica , Lípidos/análisis , Sebo/química , Adolescente , Población Negra , Mejilla , Estudios Transversales , Ácidos Grasos/análisis , Alcoholes Grasos/análisis , Femenino , Frente , Humanos , Masculino , Nigeria , Índice de Severidad de la Enfermedad , Pigmentación de la Piel , Adulto Joven
17.
Cancers (Basel) ; 13(22)2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34831015

RESUMEN

Activating mutations in the Hh pathway underlies the development of sporadic and familial skin BCC. For these oncogenic proliferations displaying ligand-independent activation of the intracellular pathway, two molecules have been approved for therapeutic purposes: vismodegib and sonidegib. Improper Hh signalling occurs in many human tumours also via a paracrine mechanism (ligand-dependent) in which the secretion of Hh ligands by stromal cells support tumour growth. On the other hand, the mobilization of neoplastic stroma by cancer cells is sustained by the activation of Hh signalling in surrounding fibroblasts suggesting a central role of this bidirectional crosstalk in carcinogenesis. Additionally, loss-of-function mutations in the PTCH1 gene in the context of NBCCS, an autosomal dominant disorder predisposing to multiple BCCs, determine tumour permissive phenotypes in dermal fibroblasts. Here, profiling syndromic and BCC-associated fibroblasts unveiled an extraordinary similarity characterized by overexpression of several Hh target genes and a marked pro-inflammatory outline. Both cell types exposed to Hh inhibitors displayed reversion of the tumour-prone phenotype. Under vismodegib and sonidegib treatment, the Wnt/ß-catenin pathway, frequently over-active in tumour stroma, resulted down-regulated by pAKT-GSK3ß axis and consequent increase of ß-catenin turnover. Overall, this study demonstrated that vismodegib and sonidegib impacting on fibroblast tumour supportive functions might be considered in therapy for BCC independently to the mutation status of Hh components in neoplastic cells.

18.
Sci Rep ; 11(1): 22906, 2021 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-34880281

RESUMEN

Bed bugs (Cimex lectularius) have proliferated globally and have become one of the most challenging pests to control indoors. They are nocturnal and use multiple sensory cues to detect and orient towards their human hosts. After feeding, usually on a sleeping human, they return to a shelter on or around the sleeping surface, but not directly on the host. We hypothesized that although human skin odors attract hungry bed bugs, human skin compounds may also prevent arrestment on hosts. We used arrestment assays to test human skin swabs, extracts from human skin swabs, and pure compounds identified from human skin swabs. When given a choice, bed bugs preferred to arrest on substrates not previously conditioned by humans. These responses were consistent among laboratory-reared and apartment-collected bed bugs. The compounds responsible for this behavior were found to be extractable in hexane, and bed bugs responded to such extracts in a dose-dependent manner. Bioassay-guided fractionation paired with thin-layer chromatography, GC-MS, and LC-MS analyses suggested that triglycerides (TAGs), common compounds found on human skin, were preventing arrestment on shelters. Bed bugs universally avoided sheltering in TAG-treated shelters, which was independent of the number of carbons or the number of double bonds in the TAG. These results provide strong evidence that the complex of human skin compounds serve as multifunctional semiochemicals for bed bugs, with some odorants attracting host-seeking stages, and others (TAGs and possibly other compounds) preventing bed bug arrestment. Host chemistry, environmental conditions and the physiological state of bed bugs likely influence the dual nature behavioral responses of bed bugs to human skin compounds.


Asunto(s)
Chinches/metabolismo , Conducta Alimentaria , Locomoción , Odorantes , Feromonas/metabolismo , Piel/parasitología , Triglicéridos/metabolismo , Adulto , Animales , Chinches/patogenicidad , Señales (Psicología) , Femenino , Interacciones Huésped-Parásitos , Humanos , Masculino , Persona de Mediana Edad , Piel/metabolismo
19.
Metabolites ; 11(12)2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34940576

RESUMEN

Lipidomics is strategic in the discovery of biomarkers of neurodegenerative diseases (NDDs). The skin surface lipidome bears the potential to provide biomarker candidates in the detection of pathological processes occurring in distal organs. We investigated the sebum composition to search diagnostic and, possibly, prognostic, biomarkers of Alzheimer's disease (AD) and Parkinson's disease (PD). The observational study included 64 subjects: 20 characterized as "probable AD with documented decline", 20 as "clinically established PD", and 24 healthy subjects (HS) of comparable age. The analysis of sebum by GCMS and TLC retrieved the amounts (µg) of 41 free fatty acids (FFAs), 7 fatty alcohols (FOHs), vitamin E, cholesterol, squalene, and total triglycerides (TGs) and wax esters (WEs). Distributions of sebum lipids in NDDs and healthy conditions were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). The deranged sebum composition associated with the PD group showed incretion of most composing lipids compared to HS, whereas only two lipid species (vitamin E and FOH14:0) were discriminant of AD samples and presented lower levels than HS sebum. Thus, sebum lipid biosynthetic pathways are differently affected in PD and AD. The characteristic sebum bio-signatures detected support the value of sebum lipidomics in the biomarkers search in NDDs.

20.
J Lipid Res ; 51(11): 3377-88, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20719760

RESUMEN

Sebum is a complex lipid mixture that is synthesized in sebaceous glands and excreted on the skin surface. The purpose of this study was the comprehensive detection of the intact lipids that compose sebum. These lipids exist as a broad range of chemical structures and concentrations. Sebum was collected with SebuTape(TM) from the foreheads of healthy donors, and then separated by HPLC on a C8 stationary phase with sub 2 µm particle size. This HPLC method provided high resolution and excellent reproducibility of retention times (RT). Compound mining was performed with time of flight (TOF) and triple quadrupole (QqQ) mass spectrometers (MS), which allowed for the classification of lipids according to their elemental composition, degree of unsaturation, and MS/MS fragmentation. The combination of the two MS systems detected 95 and 29 families of triacylglycerols (TAG) and diacylglycerols (DAG), respectively. Assignment was carried out regardless of positional isomerism. Among the wax esters (WE), 28 species were found to contain the 16:1 fatty acyl moiety. This method was suitable for the simultaneous detection of squalene and its oxygenated derivative. A total of 9 cholesterol esters (CE) were identified and more than 48 free fatty acids (FFA) were detected in normal sebum. The relative abundance of each individual lipid within its own chemical class was determined for 12 healthy donors. In summary, this method provided the first characterization of the features and distribution of intact components of the sebum lipidome.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Lípidos/análisis , Sebo/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Ésteres del Colesterol/análisis , Ésteres del Colesterol/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos/metabolismo , Femenino , Glicéridos/análisis , Glicéridos/metabolismo , Glucolípidos/análisis , Glucolípidos/metabolismo , Humanos , Masculino , Sebo/metabolismo , Escualeno/análisis , Escualeno/metabolismo , Factores de Tiempo , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA