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1.
Exp Dermatol ; 33(1): e14969, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37967213

RESUMO

Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/ß-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/ß-catenin signalling pathway and could be a potential treatment target for hair loss diseases.


Assuntos
Folículo Piloso , beta Catenina , Camundongos , Animais , Folículo Piloso/metabolismo , beta Catenina/metabolismo , Camundongos Nus , Biglicano/metabolismo , Camundongos Endogâmicos C57BL , Via de Sinalização Wnt/genética , Alopecia/metabolismo , Regeneração/fisiologia , Proliferação de Células
2.
Exp Dermatol ; 33(1): e14948, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37950506

RESUMO

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-ß-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/ß-catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.


Assuntos
Exossomos , Folículo Piloso , Humanos , Folículo Piloso/metabolismo , Derme/metabolismo , Células Cultivadas , Alopecia/metabolismo , Envelhecimento , Regeneração , Proliferação de Células
3.
Exp Dermatol ; 33(8): e15155, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39133009

RESUMO

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.


Assuntos
Fibronectinas , Glicogênio Sintase Quinase 3 beta , Folículo Piloso , Cabelo , Camundongos Endogâmicos C57BL , Via de Sinalização Wnt , beta Catenina , Animais , Humanos , Fibronectinas/metabolismo , Camundongos , Glicogênio Sintase Quinase 3 beta/metabolismo , Cabelo/crescimento & desenvolvimento , beta Catenina/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Proliferação de Células , Proteína Wnt-5a/metabolismo , Proteínas Wnt/metabolismo , Masculino , Feminino , Proteínas Proto-Oncogênicas
4.
Exp Dermatol ; 33(7): e15137, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031460

RESUMO

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.


Assuntos
Glicogênio Sintase Quinase 3 beta , Folículo Piloso , Cabelo , beta Catenina , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , Humanos , Camundongos , Cabelo/crescimento & desenvolvimento , Cabelo/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais , Colágeno/metabolismo , Fosforilação , Células Cultivadas , Peptídeos/farmacologia
5.
Lasers Med Sci ; 39(1): 251, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377836

RESUMO

Hair loss is a prevalent issue worldwide, which, though not life-threatening, can result in psychological problems, low self-esteem, and social anxiety. Previous studies have shown that ultraviolet radiation can have negative effects on hair follicle cells, leading to hair loss, while the impact of blue light on hair and hair follicle has largely been overlooked. This study aimed to examine the effects of blue light on hair follicle stem cells (HFSCs) and primary dermal papilla cells (DPCs), which are essential components of hair follicles. Human HFSCs and primary DPCs were exposed to blue light (457 nm) at various intensities (1, 4, 8, and 16 mW/cm2) for 3 days. Subsequently, cell viability, cell proliferation, and intracellular reactive oxygen species (ROS) were assessed. The results showed that blue light (457 nm) significantly reduced the cell viability and proliferation of HFSCs and DPCs in vitro, with the inhibition being intensity-dependent. Additionally, blue light triggered the overproduction of ROS in the DPCs. While the exact mechanisms by which blue light affects hair follicle cells remain unclear, these findings suggest that blue light could impede the growth of these cells. This insight may offer a new approach to protecting hair by avoiding exposure to high-intensity blue light.


Assuntos
Proliferação de Células , Sobrevivência Celular , Folículo Piloso , Espécies Reativas de Oxigênio , Células-Tronco , Folículo Piloso/efeitos da radiação , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Humanos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Células-Tronco/efeitos da radiação , Células-Tronco/fisiologia , Células Cultivadas , Luz , Derme/efeitos da radiação , Derme/citologia , Luz Azul
6.
Aesthetic Plast Surg ; 48(7): 1473-1486, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286898

RESUMO

Botulinum toxin type A (BTXA) has the potential to treat androgenetic alopecia (AGA); however, its impact on the apoptosis of dermal papillary cells (DPCs) is not yet fully understood. Noncoding RNAs play a crucial role in AGA. In this study, we investigated the potential mechanism by which BTXA alleviates apoptosis induced by dihydrotestosterone (DHT) in DPCs. We assessed the mRNA levels of circ_0135062, miR-506-3p, and Bax using qRT-PCR. Binding interactions were analyzed using RNA pulldown and dual-luciferase assays. Cell viability was determined using a cell counting kit-8 assay, and cell apoptosis was assessed using flow cytometry, TUNEL assays, and western blotting. Our findings revealed that BTXA inhibited the apoptosis of DPCs treated with DHT. Moreover, circ_0135062 overexpression counteracted the protective effect of BTXA on DHT-treated DPCs. MiR-506-3p was found to interact with Bax and inhibit apoptosis in DPCs by suppressing Bax expression in response to DHT-induced damage. Furthermore, circ_0135062 acted as a sponge for miR-506-3p, thereby inhibiting the targeting of Bax expression by miR-506-3p. In conclusion, BTXA exhibited an antiapoptotic effect on DHT-induced DPC injury via the circ_0135062/miR-506-3p/Bax axis.Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

7.
Int J Mol Sci ; 25(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39125802

RESUMO

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.


Assuntos
Proliferação de Células , Folículo Piloso , Cabelo , Estresse Oxidativo , Proliferação de Células/efeitos dos fármacos , Animais , Humanos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/citologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Antioxidantes/farmacologia , Derme/metabolismo , Derme/citologia , Derme/efeitos dos fármacos
8.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39000592

RESUMO

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.


Assuntos
Folículo Piloso , Hidroxiprostaglandina Desidrogenases , Humanos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Hidroxiprostaglandina Desidrogenases/metabolismo , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Derme/metabolismo , Derme/citologia , Derme/efeitos dos fármacos , Células Cultivadas , Via de Sinalização Wnt/efeitos dos fármacos , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Cicatrização/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia
9.
Int J Mol Sci ; 25(19)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39408700

RESUMO

With the escalating prevalence of hair loss, the demand for effective hair loss treatment has surged. This study evaluated the effects of hot water extract of Hydrangea serrata (Thunb.) Ser. leaf (WHS) on hair growth, employing cell cultures, mice, and human skin organoid models. Both WHS and hydrangenol were found to enhance 5α-reductase inhibitory activity. WHS and hydrangenol have been shown to stimulate dermal papilla cell (DPC) growth, potentially through factors like keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and transforming growth factor-ß1 (TGF-ß1). They also elevated the expression levels of keratin genes (K31 and K85) and the ceramide synthase (CerS3) gene, crucial clinical indicators of hair health. Furthermore, they exhibited notable anti-inflammatory and anti-androgenic properties by reducing the levels of tumor necrosis factor-α (TNF-α) and androgen signaling molecules, including androgen receptor (AR) and dickkopf-1 (DKK-1) gene expression. Oral administration of WHS to C57BL/6 mice for 3 weeks confirmed its hair growth-promoting effects, improving hair growth parameters and gene expression without significant changes in hair weight. Additionally, in a human skin organoid model, WHS was found to stimulate hair formation and augment the expression of follicle markers. These findings position WHS as a promising nutraceutical for promoting hair health, as evidenced by its efficacy in both in vitro and in vivo models.


Assuntos
Hydrangea , Extratos Vegetais , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Humanos , Hydrangea/química , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Camundongos Endogâmicos C57BL , Masculino , Alopecia/tratamento farmacológico
10.
Molecules ; 29(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38257211

RESUMO

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.


Assuntos
Chenopodiaceae , Fator de Crescimento Insulin-Like I , Humanos , Animais , Plantas Tolerantes a Sal , beta Catenina , Fator A de Crescimento do Endotélio Vascular , Alopecia , Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana , Extratos Vegetais/farmacologia
11.
Skin Res Technol ; 29(5): e13326, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37231925

RESUMO

BACKGROUND: When Wnt binds to the N-terminal of Frizzled, a conformational change occurs in the C-terminal of Frizzled, which binds to Dishevelled1 (Dvl1), a Wnt signaling component protein. When Dvl1 binds to the C-terminal of Frizzled, the concentration of ß-catenin increases and it enters the nucleus to transmit cell proliferation signals. CXXC-type zinc finger protein 5 (CXXC5) binds to the Frizzled binding site of Dvl1 and interferes with Dvl1-Frizzled binding. Therefore, blocking CXXC5-Dvl1 binding may induce Wnt signal transduction. MATERIALS AND METHODS: We used WD-aptamer, a DNA aptamer that specifically binds to Dvl1 and interferes with CXXC5-Dvl1 interaction. We confirmed the penetration of WD-aptamer into human hair follicle dermal papilla cells (HFDPCs) and measured ß-catenin expression following treatment with WD-aptamer in HFDPCs, wherein Wnt signaling was activated by Wnt3a. In addition, MTT assay was performed to investigate the effect of WD-aptamer on cell proliferation. RESULTS: WD-aptamer penetrated the cell, affected Wnt signaling, and increased ß-catenin expression, which plays an important role in signaling. Additionally, WD-aptamer induced HFDPC proliferation. CONCLUSION: CXXC5-associated negative feedback of Wnt/ß-catenin signaling can be regulated by interfering with CXXC5-Dvl1 interaction.


Assuntos
Aptâmeros de Nucleotídeos , Via de Sinalização Wnt , Humanos , Via de Sinalização Wnt/fisiologia , Folículo Piloso/metabolismo , beta Catenina/metabolismo , beta Catenina/farmacologia , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteínas Wnt/farmacologia , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/farmacologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia
12.
Mar Drugs ; 21(6)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367655

RESUMO

The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen).


Assuntos
Sulfatos de Condroitina , Elastina , Humanos , Sulfatos de Condroitina/farmacologia , Sulfatos de Condroitina/metabolismo , Fucose/metabolismo , Células Cultivadas , Pele , Colágeno/farmacologia , Colágeno/metabolismo , Fibroblastos/metabolismo , Dissacarídeos/metabolismo
13.
Ecotoxicol Environ Saf ; 262: 115328, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37562175

RESUMO

Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P < 0.001) and inhibited the apoptosis of DPCs (P < 0.01). VA decreased the proportion of DPCs in G0/G1 stage of the cell cycle under HS along with the expression of caspase 3, heat shock protein 70 (HSP70), and microRNA 195 (miR-195) (P < 0.05). VA also activated the insulin-like growth factor 1 (IGF1) and Wnt10b/ß-catenin signaling pathways. The results of the dual luciferase reporter assay showed that IGF1 expression was modulated by miR-195-5p. Over-expression of miR-195-5p in DPCs with HS+VA treatment significantly reduced cell viability and IGF1 signaling (P < 0.01) and increased apoptosis (P < 0.01) compared with the HS+VA group. The positive effects of VA on proliferation and apoptosis of DPCs under HS were significantly attenu-ated by blocking Wnt10b and ß-catenin signaling with IWP-2 and XAV-939, respectively. These results demonstrate that VA can promote hair follicle development following HS via modulation of miR-195/IGF1 and Wnt10b/ß-catenin signaling pathways.

14.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36834536

RESUMO

Dermal papilla cells (DPCs) play important roles in hair growth regulation. However, strategies to regrow hair are lacking. Here, global proteomic profiling identified the tetrathiomolybdate (TM)-mediated inactivation of copper (Cu) depletion-dependent mitochondrial cytochrome c oxidase (COX) as the primary metabolic defect in DPCs, leading to decreased Adenosine Triphosphate (ATP) production, mitochondrial membrane potential depolarization, increased total cellular reactive oxygen species (ROS) levels, and reduced expression of the key marker of hair growth in DPCs. By using several known mitochondrial inhibitors, we found that excessive ROS production was responsible for the impairment of DPC function. We therefore subsequently showed that two ROS scavengers, N-acetyl cysteine (NAC) and ascorbic acid (AA), partially prevented the TM- and ROS-mediated inhibition of alkaline phosphatase (ALP). Overall, these findings established a direct link between Cu and the key marker of DPCs, whereby copper depletion strongly impaired the key marker of hair growth in the DPCs by increasing excessive ROS production.


Assuntos
Derme , Folículo Piloso , Folículo Piloso/metabolismo , Células Cultivadas , Fosfatase Alcalina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Cobre/metabolismo , Proliferação de Células
15.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835374

RESUMO

Hair follicle (HF) growth and development are controlled by various cell types, including hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Exosomes are nanostructures that participate in many biological processes. Accumulating evidence indicates that DPC-derived exosomes (DPC-Exos) mediate HFSC proliferation and differentiation during the cyclical growth of hair follicles. In this study, we found that DPC-Exos increase ki67 expression and CCK8 cell viability readouts in HFSCs but reduce annexin staining of apoptotic cells. RNA sequencing of DPC-Exos-treated HFSCs identified 3702 significantly differentially expressed genes (DEGs), including BMP4, LEF1, IGF1R, TGFß3, TGFα, and KRT17. These DEGs were enriched in HF growth- and development-related pathways. We further verified the function of LEF1 and showed that overexpression of LEF1 increased the expression of HF development-related genes and proteins, enhanced HFSC proliferation, and reduced HFSC apoptosis, while knockdown of LEF1 reversed these effects. DPC-Exos could also rescue the siRNA-LEF1 effect in HFSCs. In conclusion, this study demonstrates that DPC-Exos mediated cell-to-cell communication can regulate HFSCs proliferation by stimulating LEF1 and provide novel insights into HF growth and development regulatory mechanisms.


Assuntos
Proliferação de Células , Exossomos , Folículo Piloso , Diferenciação Celular , Células Cultivadas , Exossomos/metabolismo , Folículo Piloso/citologia , Humanos
16.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37446376

RESUMO

Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α (HIF-1α) increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (BMP7). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning.


Assuntos
Células-Tronco Mesenquimais , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sistema de Sinalização das MAP Quinases , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proliferação de Células , Células-Tronco Mesenquimais/metabolismo , Hipóxia/metabolismo , Células Cultivadas , Transdução de Sinais , Fator de Crescimento Derivado de Plaquetas/farmacologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Folículo Piloso/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Meios de Cultivo Condicionados/farmacologia
17.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982775

RESUMO

Androgenic alopecia (AGA) is the most common type of hair loss, where local high concentrations of dihydrotestosterone (DHT) in the scalp cause progressive shrinkage of the hair follicles, eventually contributing to hair loss. Due to the limitations of existing methods to treat AGA, the use of multi-origin mesenchymal stromal cell-derived exosomes has been proposed. However, the functions and mechanisms of action of exosomes secreted by adipose mesenchymal stromal cells (ADSCs-Exos) in AGA are still unclear. Using Cell Counting Kit-8 (CCK8) analysis, immunofluorescence staining, scratch assays, and Western blotting, it was found that ADSC-Exos contributed to the proliferation, migration, and differentiation of dermal papilla cells (DPCs) and up-regulated the expression of cyclin, ß-catenin, versican, and BMP2. ADSC-Exos also mitigated the inhibitory effects of DHT on DPCs and down-regulated transforming growth factor-beta1 (TGF-ß1) and its downstream genes. Moreover, high-throughput miRNA sequencing and bioinformatics analysis identified 225 genes that were co-expressed in ADSC-Exos; of these, miR-122-5p was highly enriched and was found by luciferase assays to target SMAD3. ADSC-Exos carrying miR-122-5p antagonized DHT inhibition of hair follicles, up-regulated the expression of ß-catenin and versican in vivo and in vitro, restored hair bulb size and dermal thickness, and promoted the normal growth of hair follicles. So, ADSC-Exos enhanced the regeneration of hair follicles in AGA through the action of miR-122-5p and the inhibition of the TGF-ß/SMAD3 axis. These results suggest a novel treatment option for the treatment of AGA.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Folículo Piloso/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Exossomos/metabolismo , Versicanas/genética , Versicanas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Alopecia/metabolismo , Proteína Smad3/metabolismo
18.
Molecules ; 28(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37513389

RESUMO

Stem cells have demonstrated significant potential for tissue engineering and repair, anti-aging, and rejuvenation. Hair follicle stem cells can be found in the dermal papilla at the base of the follicle and the bulge region, and they have garnered increased attention because of their potential to regenerate hair as well as their application for tissue repair. In recent years, these cells have been shown to affect hair restoration and prevent hair loss. These stem cells are endowed with mesenchymal characteristics and exhibit self-renewal and can differentiate into diverse cell types. As research in this field continues, it is probable that insights regarding stem cell maintenance, as well as their self-renewal and differentiation abilities, will benefit the application of these cells. In addition, an in-depth discussion is required regarding the molecular basis of cellular signaling and the influence of nature-derived compounds in stimulating the stemness properties of dermal papilla stem cells. This review summarizes (i) the potential of the mesenchymal cells component of the hair follicle as a target for drug action; (ii) the molecular mechanism of dermal papilla stem cells for maintenance of their stem cell function; and (iii) the positive effects of the natural product compounds in stimulating stemness in dermal papilla stem cells. Together, these insights may help facilitate the development of novel effective hair loss prevention and treatment.


Assuntos
Alopecia , Folículo Piloso , Humanos , Células Cultivadas , Células-Tronco , Transdução de Sinais
19.
Int J Cosmet Sci ; 45(2): 155-165, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36411959

RESUMO

OBJECTIVE: Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C. japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C. japonica fruit shell extract (CJFSE) for hair loss mitigation. METHODS: MTT assay, spheroid culture and quantitative RT-PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT-induced hair loss were confirmed by Dkk-1 ELISA, ß-galactosidase (ß-gal) and 5α-reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. RESULTS: CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF-A, Wnt-1, c-Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α-reductase activity and DHT-induced decrease in cell proliferation, Dkk-1 secretion and ß-gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide-induced ROS production and ß-gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. CONCLUSION: CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair.


OBJECTIF: Divers facteurs sont responsables de la perte de cheveux. Souvent, les conséquences de ces facteurs se superposent et s'intensifient. Actuellement, on étudie comment atténuer la perte de cheveux en faisant proliférer les cellules de la papille dermique (DPC) et en inhibant les facteurs délétères tels que la dihydrotestostérone (DHT) et le stress oxydatif sur la croissance des cheveux. La coque du fruit du Camélia du Japon (Camelia japonica) est habituellement rejetée. Son utilité biologique reste à élucider. Dans cette étude, nous avons étudié la capacité de l'extrait de la coque du fruit du Camélia du Japon (CJFSE) dans la mitigation de la perte de cheveux. MÉTHODES: Un test MTT, une culture de sphéroïdes et une RT-PCR Quantitative ont été effectués pour observer la prolifération de CJFSE sur les cellules de la papille dermique du follicule pileux (HFDPC). Les effets du CJFSE sur la perte de cheveux induite par la DHT ont été confirmés par Dkk-1 ELISA, ß-galactosidase (ß-gal) et 5α-réductase. De plus, les effets du CJFSE sur le stress oxydatif ont été confirmés par des tests de production de DPPH et de ROS. RÉSULTATS: Le CJFSE a augmenté la prolifération et la taille sphéroïde des HFDPC. Les niveaux d'expression de VEGF-A, Wnt-1, c-Myc et cycline D1 ont été régulés de manière efficace par le CJFSE. Le CJFSE a également supprimé l'activité de la 5α-réductase et a induit la réduction de la DHT et de la prolifération cellulaire, ainsi que de la sécrétion de Dkk-1 et de l'activité ß-gal. Le CJFSE a en outre montré une activité de capture du DPPH et amélioré la production de ROS induite par le peroxyde d'hydrogène et l'activité ß-gal. Pour finir, les acides gallique et protocatéchuique ont été observés dans le CJFSE après analyse des HPLC. CONCLUSION: Le CJFSE a le potentiel d'atténuer la perte de cheveux en favorisant la croissance des cellules ciliées et en supprimant les effets de la DHT et du stress oxydatif sur les cheveux.


Assuntos
Alopecia , Frutas , Espécies Reativas de Oxigênio , Di-Hidrotestosterona/efeitos adversos , Extratos Vegetais/farmacologia , Oxirredutases
20.
BMC Genomics ; 23(1): 527, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864447

RESUMO

BACKGROUND: Cashmere goats are a heterogeneous hairy mammal. The fineness of cashmere can affect its economic value. Therefore, in this study, we used transcriptome sequencing techniques to analyze the gene expression profiles of the skin tissues of cashmere goats with different cashmere fineness. The selected candidate genes were functionally verified with the secondary hair follicle hair papillary cells of cashmere goats. RESULTS: We identified 479 DEGs, of which 238 mRNAs were up-regulated in the fine velvet group and 241 mRNA were down-regulated. Based on functional annotation and protein interaction network analysis, we found some genes that may affect the fineness of cashmere, including SOX18, SOX4, WNT5A, IGFBP4, KAP8, KRT36, and FA2H. Using qRT-PCR, Western blot, CCK-8 cell viability detection, EDU cell proliferation detection, and flow cytometry, we found that overexpression of the FA2H gene could promote the proliferation of secondary hair follicle DPCs in cashmere goats. At the same time, we proved that FA2H could regulate the expression levels of the FGF5 and BMP2 genes in DPCs. CONCLUSION: The results of this study provide a useful reference for the genetics and breeding of Jiangnan cashmere goats and goat genome annotation, and provide an experimental basis for improving cashmere quality of the cashmere goat.


Assuntos
Cabras , Transcriptoma , Animais , Cabras/genética , Cabras/metabolismo , Cabelo , Folículo Piloso/metabolismo , RNA Mensageiro/genética
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