RESUMEN
Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/ß-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/ß-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/ß-catenin pathway and highlight its therapeutic potential in hair loss treatment.
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Fibronectinas , Glucógeno Sintasa Quinasa 3 beta , Folículo Piloso , Cabello , Ratones Endogámicos C57BL , Vía de Señalización Wnt , beta Catenina , Animales , Humanos , Fibronectinas/metabolismo , Ratones , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Cabello/crecimiento & desarrollo , beta Catenina/metabolismo , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/metabolismo , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Proliferación Celular , Proteína Wnt-5a/metabolismo , Proteínas Wnt/metabolismo , Masculino , Femenino , Proteínas Proto-OncogénicasRESUMEN
The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H2O2-mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss.
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Proliferación Celular , Folículo Piloso , Cabello , Estrés Oxidativo , Proliferación Celular/efectos de los fármacos , Animales , Humanos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/citología , Ratones , Estrés Oxidativo/efectos de los fármacos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Antioxidantes/farmacología , Dermis/metabolismo , Dermis/citología , Dermis/efectos de los fármacosRESUMEN
The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread. A potential correlation between the onset of BCC and a dysembryogenetic process has long been hypothesised. A selective investigation of PubMed-indexed publications supporting this theory retrieved 64 selected articles published between 1901 and 2024. From our analysis of the literature review, five main research domains on the dysembryogenetic pathogenesis of BCC were identified: (1) The correlation between the topographic distribution of BCC and the macroscopic embryology, (2) the correlation between BCC and the microscopic embryology, (3) the genetic BCC, (4) the correlation between BCC and the hair follicle and (5) the correlation between BCC and the molecular embryology with a specific focus on the Hedgehog signalling pathway. A large amount of data from microscopic and molecular research consistently supports the hypothesis of a dysembryogenetic pathogenesis of BCC. Such evidence is promoting advances in the clinical management of this disease, with innovative targeted molecular therapies on an immune modulating basis being developed.
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Carcinoma Basocelular , Proteínas Hedgehog , Neoplasias Cutáneas , Carcinoma Basocelular/patología , Carcinoma Basocelular/etiología , Carcinoma Basocelular/genética , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/etiología , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Transducción de Señal , Folículo Piloso/patología , Folículo Piloso/embriología , Folículo Piloso/metabolismoRESUMEN
Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.
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Colitis Ulcerosa , Modelos Animales de Enfermedad , Exosomas , Folículo Piloso , Células Madre Mesenquimatosas , Mitofagia , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/terapia , Colitis Ulcerosa/patología , Células Madre Mesenquimatosas/metabolismo , Exosomas/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Folículo Piloso/metabolismo , Sulfato de Dextran , Masculino , Mitocondrias/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , MicroARNs/genética , HumanosRESUMEN
AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3ß(Ser9) and ß-catenin(Ser675), indicating the activation of the GSK-3ß/ß-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health.
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Glucógeno Sintasa Quinasa 3 beta , Folículo Piloso , Cabello , beta Catenina , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , beta Catenina/metabolismo , Humanos , Ratones , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Proliferación Celular/efectos de los fármacos , Transducción de Señal , Colágeno/metabolismo , Fosforilación , Células Cultivadas , Péptidos/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ecliptea herba, a traditional Chinese herbal medicine for hair loss, was first recorded in the Tang Dynasty's 'Qian Jin Yue Ling', of which the active ingredients and mechanisms of action in the treatment of chemotherapy-induced hair loss remain poorly investigated. AIM OF THE STUDY: To investigate the effects of the petroleum ether extract of Eclipta (PEE) on alopecia and follicle damage and elucidate its potential therapeutic mechanisms using the integration of network pharmacology, bioinformatics, and experimental validation. MATERIALS AND METHODS: UPLC-MS was used to analyse the chemical composition of PEE. A network pharmacology approach was employed to establish the 'components-targets-pathways' network of PEE to explore potential therapeutic pathways and targets. Molecular docking was used for validation, and the mechanism of PEE in treating chemotherapy-induced alopecia (CIA) was elucidated using in vitro and in vivo on CIA models. RESULTS: UPLC-MS analysis of PEE revealed 185 components, while network pharmacology and molecular docking analyses revealed potential active compounds and their target molecules, suggesting the involvement of core genes, such as TP53, ESR1, AKT1, IL6, TNF, and EGFR. The key components included wedelolactone, dimethyl-wedelolactone, luteoloside, linarin, and hispidulin. In vivo, PEE promoted hair growth, restored the number of hair follicles, and reduced follicle apoptosis. Conversely, in vitro, PEE enhanced cell viability, reduced apoptosis, and protected HaCaT cells from damage induced by 4-hydroperoxycyclophosphamide (4-HC). CONCLUSIONS: PEE alleviated hair follicle damage in CIA mice by inhibiting the P53/Fas pathway, which may be associated with inhibiting hair follicle cell apoptosis. This study provides a novel therapeutic strategy for treating cyclophosphamide-induced hair loss.
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Alopecia , Eclipta , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Alcanos , Alopecia/inducido químicamente , Alopecia/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Ciclofosfamida/toxicidad , Eclipta/química , Células HaCaT , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales/farmacología , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.
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Adenosina , Alopecia , Folículo Piloso , Cabello , Minoxidil , Receptores Androgénicos , Transducción de Señal , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Alopecia/patología , Humanos , Masculino , Receptores Androgénicos/metabolismo , Adenosina/metabolismo , Adenosina/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Transducción de Señal/efectos de los fármacos , Minoxidil/farmacología , Femenino , Animales , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Cabello/metabolismoRESUMEN
Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary cicatricial alopecia that cause a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. They are characterized by permanent loss of hair follicle stem cells (HFSCs) by pathomechanisms still poorly understood, resulting in poor efficacy of currently available treatments. Caveolae are flask-shaped lipid rafts invaginated within the plasma membrane of multiple cell types. Although their role in the HF physiology and pathophysiology is relatively unknown, we have previously demonstrated that the primary structural component of caveolae (caveolin-1 or Cav1) is upregulated in FFA. Thus, we propose to investigate the expression and localization of caveolae-associated structural proteins (Cav1, Cav2, and Cavin-1) and HFSCs (identified by K15) in both LPP and FFA. We analyzed 4 patients with LPP biopsied in affected and non-affected (NA) scalp, 4 patients with FFA biopsied in affected scalp and 4 healthy controls. Affected scalp of LPP and FFA demonstrated increased levels of Cav1 and Cavin-1 compared with HC and LPP-NA. Moreover, Cav1, Cav2 and Cavin1 all exhibit high colocalization with K15 and their expression appears to be negatively correlated, supporting the hypothesis that these proteins are important players in LPP/FFA and may serve as therapeutic targets in future treatments.
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Alopecia , Caveolas , Caveolina 1 , Folículo Piloso , Liquen Plano , Regulación hacia Arriba , Humanos , Alopecia/patología , Alopecia/metabolismo , Folículo Piloso/patología , Folículo Piloso/metabolismo , Liquen Plano/metabolismo , Liquen Plano/patología , Persona de Mediana Edad , Femenino , Caveolina 1/metabolismo , Masculino , Caveolas/metabolismo , Cuero Cabelludo/patología , Adulto , Queratina-15/metabolismo , Anciano , Biopsia , Fibrosis , Células Madre/metabolismo , Células Madre/patología , Proteínas de Unión al ARN/metabolismoRESUMEN
While many gene expression studies have focused on male pattern baldness (MPB), few studies have investigated the genetic differences between bald and non-bald hair follicles in female pattern hair loss (FPHL). This study aimed to identify molecular biomarkers associated with FPHL through genetic analysis of paired bald and non-bald hair follicles from 18 FPHL patients, using next-generation sequencing (NGS) techniques. RNA transcriptome analysis was performed to identify differentially expressed genes (DEGs) between bald and non-bald hair follicles in FPHL. The DEGs were validated using real-time PCR, and protein expression was confirmed through immunohistochemistry and western blot analysis. Our findings suggest that HOXB13, SFRP2, PTGDS, CXCR3, SFRP4, SOD3, and DCN are significantly upregulated in bald hair follicles compared to non-bald hair follicles in FPHL. SFRP2 and PTGDS were found to be consistently highly expressed in bald hair follicles in all 18 samples. Additionally, elevated protein levels of SFRP2 and PTGDS were confirmed through western blot and immunohistochemical analysis. Our study identified SFRP2 and PTGDS as potential biomarkers for FPHL and suggests that they may play a role in inducing hair loss in this condition. These findings provide a foundation for further research on the pathogenesis of FPHL and potential therapeutic targets.
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Alopecia , Pueblo Asiatico , Perfilación de la Expresión Génica , Folículo Piloso , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Alopecia/genética , Alopecia/patología , Pueblo Asiatico/genética , Folículo Piloso/metabolismo , Folículo Piloso/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas , Cuero Cabelludo/patología , TranscriptomaRESUMEN
Hypotrichosis is a genetic disorder characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in a disintegrin and a metalloproteinase domain 17 (ADAM17) gene caused hypotrichosis with woolly hair. Adam17 (p.D647N) knockin mice mimicked the hair abnormality in patients. ADAM17 (p.D647N) mutation led to hair follicle stem cell (HFSC) exhaustion and caused abnormal hair follicles, ultimately resulting in alopecia. Mechanistic studies revealed that ADAM17 binds directly to E3 ubiquitin ligase tripartite motif-containing protein 47 (TRIM47). ADAM17 variant enhanced the association between ADAM17 and TRIM47, leading to an increase in ubiquitination and subsequent degradation of ADAM17 protein. Furthermore, reduced ADAM17 protein expression affected the Notch signaling pathway, impairing the activation, proliferation, and differentiation of HFSCs during hair follicle regeneration. Overexpression of Notch intracellular domain rescued the reduced proliferation ability caused by Adam17 variant in primary fibroblast cells.
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Proteína ADAM17 , Alopecia , Folículo Piloso , Ubiquitina-Proteína Ligasas , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Animales , Alopecia/genética , Alopecia/metabolismo , Alopecia/patología , Ratones , Folículo Piloso/metabolismo , Folículo Piloso/patología , Humanos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Masculino , Transducción de Señal/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Femenino , Mutación , Técnicas de Sustitución del Gen , Proliferación Celular/genética , Diferenciación Celular/genética , Proteolisis , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genéticaRESUMEN
Objective: To summarize the dynamic and synchronized changes between the hair cycle and dermal adipose tissue as well as the impact of dermal adipose tissue on hair growth, and to provide a new research idea for the clinical treatment of hair loss. Methods: An extensive review of relevant literature both domestic and international was conducted, analyzing and summarizing the impact of dermal adipose precursor cells, mature dermal adipocytes, and the processes of adipogenesis in dermal adipose tissue on the transition of hair cycle phases. Results: Dermal adipose tissue is anatomically adjacent to hair follicles and closely related to the changes in the hair cycle. The proliferation and differentiation of dermal adipose precursor cells promote the transition of hair cycle from telogen to anagen, while mature adipocytes can accelerate the transition from anagen to catagen of the hair cycle by expressing signaling molecules, with adipogenesis in dermal adipose tissue and hair cycle transition signaling coexistence. Conclusion: Dermal adipose tissue affects the transition of the hair cycle and regulates hair growth by secreting various signaling molecules. However, the quantity and depth of existing literature are far from sufficient to fully elucidate its prominent role in regulating the hair cycle, and the specific regulatory mechanisms needs to be further studied.
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Tejido Adiposo , Diferenciación Celular , Cabello , Animales , Humanos , Adipocitos/citología , Adipocitos/metabolismo , Adipogénesis , Tejido Adiposo/metabolismo , Tejido Adiposo/citología , Alopecia/metabolismo , Proliferación Celular , Dermis/metabolismo , Dermis/citología , Cabello/crecimiento & desarrollo , Cabello/metabolismo , Folículo Piloso/metabolismo , Transducción de SeñalRESUMEN
Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.
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Cabello , Aceites , Animales , Femenino , Ratones , Biología Computacional/métodos , Proteínas Filagrina , Perfilación de la Expresión Génica/métodos , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Cabello/metabolismo , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Ratones Endogámicos C57BL , Minoxidil/administración & dosificación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Ballenas , Aceites/administración & dosificaciónRESUMEN
Tissue regeneration and maintenance rely on coordinated stem cell behaviours. This orchestration can be impaired by oncogenic mutations leading to cancer. However, it is largely unclear how oncogenes perturb stem cells' orchestration to disrupt tissue. Here we used intravital imaging to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking hair follicles in live mice, we found that KrasG12D, a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner, linked with abnormal cell division and migration. Using a reporter mouse capture real-time ERK signal dynamics at the single-cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts ERK signal in stem cells from pulsatile to sustained. Finally, we demonstrated that interrupting sustained ERK signal reverts KrasG12D-induced tissue deformation through modulating specific features of cell migration and division.
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Movimiento Celular , Folículo Piloso , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Animales , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ratones , Folículo Piloso/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Ratones Transgénicos , Células Madre/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Humanos , Femenino , Activación EnzimáticaRESUMEN
Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.
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Alopecia , Cuernos de Venado , Proteína Morfogenética Ósea 4 , Folículo Piloso , Cabello , Animales , Cuernos de Venado/química , Alopecia/tratamiento farmacológico , Alopecia/patología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Ratones , Masculino , Proteína Morfogenética Ósea 4/metabolismo , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Proteínas Hedgehog/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Extractos de Tejidos/farmacología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Regeneración/efectos de los fármacos , Ciervos , Proteína Smad5/metabolismoRESUMEN
Dermal papilla cell (DPC) belongs to a specialized mesenchymal stem cell for hair follicle regeneration. Maintaining the ability of DPCs to stimulate hair in vitro culture is important for hair follicle morphogenesis and regeneration. As the third generation of platelet concentrate, injectable platelet-rich fibrin (i-PRF) is a novel biomaterial containing many growth factors and showing promising effects on tissue reconstruction. We aimed to explore the influences of i-PRF on the proliferative, migratory, as well as trichogenic ability of DPCs and compared the effects of i-PRF and platelet-rich plasma (PRP), the first generation of platelet concentrate. Both PRP and i-PRF facilitated DPCs proliferation, and migration, along with trichogenic inductivity as well as stimulated the TGF-ß/Smad pathway, while the impacts of i-PRF were more significant than PRP. A small molecule inhibitor of TGF-beta receptor I, Galunisertib, was also applied to treat DPCs, and it rescued the impacts of i-PRF on the proliferative, migratory, trichogenic inductivity, and proteins-associated with TGF-ß/Smad pathway in DPCs. These findings revealed that i-PRF had better effects than PRP in enhancing the proliferative, migratory, and hair-inducing abilities of DPCs by the TGF-ß/Smad pathway, which indicated the beneficial role of i-PRF in hair follicle regeneration.
Asunto(s)
Movimiento Celular , Proliferación Celular , Folículo Piloso , Fibrina Rica en Plaquetas , Transducción de Señal , Proteínas Smad , Factor de Crecimiento Transformador beta , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/citología , Proteínas Smad/metabolismo , Humanos , Fibrina Rica en Plaquetas/metabolismo , Movimiento Celular/efectos de los fármacos , Dermis/citología , Dermis/metabolismo , Dermis/efectos de los fármacos , Células Cultivadas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Plasma Rico en Plaquetas/metabolismo , InyeccionesRESUMEN
BACKGROUND/AIM: Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation. MATERIALS AND METHODS: Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography. RESULTS: After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine. CONCLUSION: Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem cells.
Asunto(s)
Folículo Piloso , Cabello , Homocisteína , Metionina , Animales , Metionina/deficiencia , Metionina/metabolismo , Metionina/administración & dosificación , Ratones , Cabello/crecimiento & desarrollo , Cabello/metabolismo , Homocisteína/metabolismo , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Ratones Endogámicos C57BL , Alopecia/metabolismo , Alopecia/etiología , Alopecia/patología , Modelos Animales de Enfermedad , Dieta , Queratinocitos/metabolismoRESUMEN
Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45- cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., Kit+, Cd34+/-, Plp1+, Cd274+/-, Thy1+, Cdh3+/-) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.
Asunto(s)
Melanocitos , Ratones Endogámicos C57BL , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Células Madre , Animales , Melanocitos/metabolismo , Melanocitos/citología , Células Madre/metabolismo , Células Madre/citología , Femenino , Ratones , Diferenciación Celular , Folículo Piloso/citología , Folículo Piloso/metabolismo , Heterogeneidad GenéticaRESUMEN
Chemotherapy-induced alopecia (CIA) represents one of the most severe side effects of chemotherapy, which forces some patients to reject cancer treatment. The exact pathophysiological mechanisms of CIA are not clearly understood, which makes it difficult to discover efficient preventive or therapeutic procedures for this adverse effect. N-acetylcysteine (NAC) has a strong antioxidant activity as it stimulates glutathione synthesis and acts as an oxygen radical scavenger. The current study tried to investigate the efficacy of NAC in preserving biochemical parameters and hair follicle structure against cyclophosphamide (CYP) administration. In total, 40 adult female C57BL/6 mice were induced to enter anagen by depilation (day 0) and divided into four groups: group I (control), group II (CYP) received a single dose of CYP [150 mg/kg body weight (B.W.)/intraperitoneal injection (IP)] at day 9, group III (CYP & NAC) received a single dose of CYP at day 9 as well as NAC (500 mg/kg B.W./day/IP) from day 6-16, and group IV (NAC) received NAC from day 6-16. CYP administration in group II induced an increase in malondialdehyde (MDA), decrease in superoxide dismutase (SOD), histological hair follicle dystrophy, disruption of follicular melanogenesis, overexpression of p53, and loss of ki67 immunoreactivity. NAC coadministration in group III reversed CYP-induced alterations in the biochemical parameters and preserved hair follicle structure, typical follicular melanin distribution as well as normal pattern of p53 and ki67 expression. These findings indicated that NAC could be used as an efficient and safe therapeutic option for hair loss induced by chemotherapy.
Asunto(s)
Acetilcisteína , Alopecia , Ciclofosfamida , Modelos Animales de Enfermedad , Folículo Piloso , Ratones Endogámicos C57BL , Animales , Alopecia/inducido químicamente , Alopecia/tratamiento farmacológico , Alopecia/patología , Alopecia/metabolismo , Ratones , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/patología , Femenino , Acetilcisteína/farmacología , Antineoplásicos AlquilantesRESUMEN
Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of ß-Catenin. Since several anagen-inductive genes are regulated by ß-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated ß-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3ß/ß-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H2O2)-induced HDPCs. The senescence-associated ß-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H2O2-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.
Asunto(s)
Glucógeno Sintasa Quinasa 3 beta , Peróxido de Hidrógeno , Estrés Oxidativo , Floroglucinol , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , beta Catenina , Humanos , Floroglucinol/farmacología , Floroglucinol/análogos & derivados , Estrés Oxidativo/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Transducción de Señal/efectos de los fármacos , beta Catenina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fosforilación/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/citología , Dermis/citología , Dermis/metabolismo , Dermis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Alopecia/tratamiento farmacológico , Alopecia/metabolismoRESUMEN
Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of ß-catenin. We confirmed that 100 nM tegatrabetan (TG), a ß-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3ß and Akt, translocation of ß-catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, ß-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing ß-catenin-mediated hair growth.