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1.
Gene ; 731: 144338, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31923576

RESUMO

The primary feather follicles are universal skin appendages widely distributed in the skin of feathered birds. The morphogenesis and development of the primary feather follicles in goose skin remain largely unknown. Here, the induction of primary feather follicles in goose embryonic skin (pre-induction vs induction) was investigated by de novo transcriptome analyses to reveal 409 differentially expressed genes (DEGs). The DEGs were characterized to potentially regulate the de novo formation of feather follicle primordia consisting of placode (4 genes) and dermal condensate (12 genes), and the thickening of epidermis (5 genes) and dermal fibroblasts (17 genes), respectively. Further analyses enriched DEGs into GO terms represented as cell adhesion and KEGG pathways including Wnt and Hedgehog signaling pathways that are highly correlated with cell communication and molecular regulation. Six selected Wnt pathway genes were detected by qPCR with up-regulation in goose skin during the induction of primary feather follicles. The localization of WNT16, SFRP1 and FRZB by in situ hybridization showed weak expression in the primary feather primordia, whereas FZD1, LEF1 and DKK1 were expressed initially in the inter-follicular skin and feather follicle primordia, then mainly restricted in the feather primordia. The spatial-temporal expression patterns indicate that Wnt pathway genes DKK1, FZD1 and LEF1 are the important regulators functioned in the induction of primary feather follicle in goose skin. The dynamic molecular changes and specific gene expression patterns revealed in this report provide the general knowledge of primary feather follicle and skin development in waterfowl, and contribute to further understand the diversity of hair and feather development beyond the mouse and chicken models.


Assuntos
Plumas/embriologia , Gansos , Genes Controladores do Desenvolvimento , Folículo Piloso/embriologia , Morfogênese/genética , Pele/embriologia , Animais , Embrião de Galinha , Embrião não Mamífero , Desenvolvimento Embrionário/genética , Plumas/metabolismo , Gansos/embriologia , Gansos/genética , Gansos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Controladores do Desenvolvimento/genética , Folículo Piloso/metabolismo , Pele/metabolismo
2.
PLoS One ; 14(12): e0216104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31841509

RESUMO

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.


Assuntos
/farmacologia , Receptor CB2 de Canabinoide/efeitos dos fármacos , Cicatrização/fisiologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Folículo Piloso/metabolismo , Inflamação/tratamento farmacológico , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reepitelização , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Sesquiterpenos/metabolismo , Fatores Sexuais , Pele/metabolismo , Cicatrização/efeitos dos fármacos
3.
BMC Complement Altern Med ; 19(1): 372, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847849

RESUMO

BACKGROUND: Vernonia anthelmintica (L.) willd is a traditional urgur herb in China for a long history. Its alcohol extract (AVE) has been proved to promote hair follicle growth in C57BL/6 mice. We conducted this study to investigate the hair-growth effects of AVE in stressed mice and its possible mechanism of action. METHODS: The hair-follicle growth effects of AVE were examined by in vivo and in vitro study. We exposed C57BL/6 male mice to chronic restraint stress to induce murine hair follicle growth inhibition. The effects of AVE were examined by histological analysis, immunofluorescence for Ki67 and cytokeratin 19 immunoreactivity, western blot assay in tyrosinase and related proteins expressions and immunofluorescence for nerve fibers. In organ culture of mouse vibrissae follicles, we used substance P as a catagen-inducing factor of hair follicle growth, and measured the elongation of hair shafts and expression of neurokinin-1 receptor protein by application of AVE. RESULTS: Our results showed that AVE counteract murine hair follicle growth inhibition caused by chronic restraint stress via inducing the conversion of telogen to anagen and inhibiting catagen premature, increasing bulb keratinocytes and bulge stem cells proliferation, promoting melanogenesis, and reducing the numbers of substance P and calcitonin gene-related peptide nerve fibers. Furthermore, AVE also counteracted murine hair follicle growth inhibition caused by substance P in organ culture. CONCLUSION: These results suggest that AVE counteract stress-induced hair follicle growth inhibition in C57BL/6 mice in vivo and in vitro, and may be an effective new candidate for treatment of stress-induced hair loss.


Assuntos
Folículo Piloso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Vernonia , Animais , Folículo Piloso/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Restrição Física
4.
Zhonghua Shao Shang Za Zhi ; 35(10): 740-745, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31658545

RESUMO

Objective: To construct and identify a mouse model with conditional knockout (cKO) of p75 neurotrophin receptor (p75NTR-cKO) gene in epidermis cells by Cre-loxP system. Methods: Five p75NTR(flox/flox) transgenic C57BL/6J mice (aged 6-8 weeks, male and female unlimited, the age and sex of mice used for reproduction were the same below) and five keratin 14 promotor-driven (KRT14-) Cre(+ /-) transgenic C57BL/6J mice were bred and hybridized via Cre-loxP system. Five p75NTR(flox/+) ·KRT14-Cre(+ /-) mice selected from the first generation of mice were mated with five p75NTR(flox/flox) mice to obtain the second generation hybrids. After the second generation mice were born 20-25 days, the parts of the mice tail were cut off to identify the genotype by polymerase chain reaction method. Four p75NTR gene complete cKO mice (6 weeks old) and 4 wild-type mice (6 weeks old) were selected and sacrificed respectively. The abdominal skin tissue and brain tissue were excised to observe the expression of p75NTR in the two tissue of two types of mice by immunohistochemical staining. The abdominal skin tissue of two types of mice was obtained to observe the histomorphological changes by hematoxylin and eosin staining. Results: (1) Twenty second generation mice were bred. The genotype of 4 mice was p75NTR(flox/flox)·KRT14-Cre(+ /-)(p75NTR(-/-)), i. e. p75NTR gene complete cKO mice; the genotype of 5 mice was p75NTR(flox/+) ·KRT14-Cre(+ /-), i. e. p75NTR gene partial cKO mice; the genotype of 5 mice was p75NTR(flox/flox)·KRT14-Cre(-/-), and that of 6 mice was p75NTR(flox/+) ·KRT14-Cre(-/-), all of which were wild-type mice. (2) The expression of p75NTR was negative in skin epidermis tissue of p75NTR gene complete cKO mice, while numerous p75NTR positive expression was observed in skin epidermis tissue of wild-type mice. Abundant p75NTR positive expression was observed in brain tissue of both wild-type mice and p75NTR gene complete cKO mice. (3) There was no abnormal growth of skin epidermis tissue in both wild-type mice and p75NTR gene complete cKO mice, with intact hair follicle structure. Conclusions: Applying Cre-loxP system can successfully construct a p75NTR-cKO mice model in epidermis cells without obvious changes in skin histomorphology.


Assuntos
Células Epidérmicas , Folículo Piloso/crescimento & desenvolvimento , Receptor de Fator de Crescimento Neural , Animais , Feminino , Folículo Piloso/metabolismo , Integrases , Queratina-14 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
Drug Dev Ind Pharm ; 45(10): 1654-1663, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382790

RESUMO

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia. Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies. Key findings: Hybrid NPs had mean vesicles size 339 ± 1.6, zeta potential -32.6 ± 0.51, and entrapment efficiency 78 ± 5.5. Cumulative drug release after 12 h was found to be 47.27 ± 0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis. Conclusion: This study concludes that phospholipid-polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.


Assuntos
Alopecia/tratamento farmacológico , Folículo Piloso/metabolismo , Nanopartículas/química , Fosfolipídeos/química , Polímeros/química , Quercetina/metabolismo , Quercetina/farmacologia , Animais , Varredura Diferencial de Calorimetria/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Masculino , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
7.
Tissue Cell ; 59: 33-38, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383286

RESUMO

Hair-follicle-associated pluripotent (HAP) stem cells reside in the upper part of the bulge area of the the hair follicle. HAP stem cells are nestin-positive and keratin 15-negative and have the capacity to differentiate into various types of cells in vitro. HAP stem cells are also involved in nerve and spinal cord regeneration in mouse models. Recently, it was shown that the DNA-damage response in non-HAP hair follicle stem cells induces proteolysis of type-XVII collagen (COL17A1/BP180), which is involved in hair-follicle stem-cell maintenance. COL17A1 proteolysis stimulated hair-follicle stem-cell aging, characterized by the loss of stemness signatures and hair-follicle miniaturization associated with androgenic alopecia. In the present study, we demonstrate that HAP stem cells co-express nestin and COL17A1 in vitro and in vivo. The expression of HAP stem cell markers (nestin and SSEA1) increased after HAP stem-cell colonies were formed, then decreased after differentiation to epidermal keratinocytes. In contrast COL17A1 increased after differentiation to epidermal keratinocytes. These results suggest that COL17A1 is important in differentiation of HAP stem cells.


Assuntos
Autoantígenos/biossíntese , Diferenciação Celular , Regulação da Expressão Gênica , Folículo Piloso/metabolismo , Queratinócitos/metabolismo , Colágenos não Fibrilares/biossíntese , Células-Tronco Pluripotentes/metabolismo , Animais , Antígenos de Diferenciação/biossíntese , Folículo Piloso/citologia , Queratinócitos/citologia , Camundongos , Nestina/biossíntese , Células-Tronco Pluripotentes/citologia
8.
J Dermatol ; 46(9): 794-797, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294481

RESUMO

We report a case of kerion celsi due to Trichophyton tonsurans. An 18-year-old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human ß-defensin 2 (HBD-2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)-17A generally induces HBD-2 production by epidermal keratinocytes, we also immunohistochemically investigated IL-17A expression. Unexpectedly, many IL-17A-bearing cells were found around destructed hair follicles, indicating that IL-17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL-17A-upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL-17A may cause tissue damage and resultant scar.


Assuntos
Interleucina-17/metabolismo , Tinha do Couro Cabeludo/imunologia , Trichophyton/imunologia , beta-Defensinas/metabolismo , Adolescente , Biópsia , Folículo Piloso/imunologia , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Interleucina-17/imunologia , Masculino , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/patologia , Trichophyton/isolamento & purificação , beta-Defensinas/imunologia
9.
Biochem Genet ; 57(5): 734-744, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302800

RESUMO

Animal melanin has an important role in the formation of animal fur and skin, which is determined by its quantities, character, and distribution. To identify the effect of melanin on the formation of multi-colored Rex rabbits (Black, Chinchilla, Beaver, Protein cyan, Protein yellow, White), the structure of hair follicles and melanin content in multi-colored Rex rabbit skins were observed by Hematoxylin and Eosin (H&E) staining and melanin staining, respectively. The melanin granules were primarily found in the epidermis and hair follicle roots. The melanin content of skin was measured by extracting melanin from skin tissue. The results demonstrated that the melanin content was the highest in the skin of black Rex rabbit. Additionally, we measured the mRNA and protein expression levels of melanin-related key genes (MITF and TYR) in the skin of different hair color by quantitative real-time PCR and Wes assay, respectively. The results revealed that the mRNA expression levels in the skin of black Rex rabbit was highly expressed when as compared with other Rex rabbit skin (P < 0.01), and they were the lowest in the skin of white Rex rabbit. Finally, correlation analysis was conducted between melanin content and the expression levels of mRNA and protein. The results indicated a significant correlation between melanin content and the mRNA expression of MITF (P < 0.05), but it was not correlated with the mRNA expression of TYR (P > 0.05). In summary, melanin deposition has important economic value, and the coat color of fur-bearing animals is partly determined by the melanin-related genes.


Assuntos
Regulação da Expressão Gênica/fisiologia , Folículo Piloso/metabolismo , Melaninas/biossíntese , Pigmentação da Pele/fisiologia , Animais , Coelhos
10.
PLoS One ; 14(7): e0219938, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31335913

RESUMO

Podoplanin (PDPN) is a glycoprotein that is expressed by various cell types, including keratinocytes, fibroblasts, and lymphatic endothelial cells. We found that PDPN is expressed in the hair follicle (HF) keratinocyte region and HF stem cell area during the late anagen phase but not during the telogen phase in mice. Importantly, keratinocyte-specific PDPN deletion in mice (K5-Cre;PDPNflox/flox) promoted anagen HF growth after depilation-induced HF regeneration as compared to control mice. RNA sequencing, followed by gene ontology analysis, showed down-regulation of focal adhesion and extracellular matrix interaction pathways in HF stem cells isolated from K5-Cre;PDPNflox/flox mice as compared to control mice. Furthermore, HF keratinocytes isolated from K5-Cre;PDPNflox/flox mice exhibited a decreased ability to interact with collagen type I in cell adhesion assays. Taken together, these results show that PDPN deletion promotes HF cycling, possibly via reduced focal adhesion and concomitantly enhanced migration of HF stem cells towards the bulb region. They also indicate potential new therapeutic strategies for the treatment of conditions associated with hair loss.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Glicoproteínas de Membrana/metabolismo , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/fisiologia , Animais , Movimento Celular , Células Cultivadas , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Feminino , Adesões Focais/metabolismo , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinócitos/fisiologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL
11.
BMC Genomics ; 20(1): 512, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221080

RESUMO

BACKGROUND: Dermal papilla cells (DPCs), the "signaling center" of hair follicle (HF), delicately master continual growth of hair in mammals including cashmere, the fine fiber annually produced by secondary HF embedded in cashmere goat skins. Such unparalleled capacity bases on their exquisite character in instructing the cellular activity of hair-forming keratinocytes via secreting numerous molecular signals. Past studies suggested microRNA (miRNAs) and long non-coding RNAs (lncRNAs) play essential roles in a wide variety of biological process, including HF cycling. However, their roles and related molecular mechanisms in modulating DPCs secretory activities are still poorly understood. RESULTS: Here, we separately cultivated DPCs and their functionally and morphologically distinct dermal fibroblasts (DFs) from cashmere goat skins at anagen. With the advantage of high throughput RNA-seq, we synchronously identified 2540 lncRNAs and 536 miRNAs from two types of cellular samples at 4th passages. Compared with DFs, 1286 mRNAs, 18 lncRNAs, and 42 miRNAs were upregulated, while 1254 mRNAs, 53 lncRNAs and 44 miRNAs were downregulated in DPCs. Through overlapping with mice data, we ultimately defined 25 core signatures of DPCs, including HOXC8 and RSPO1, two crucial activators for hair follicle stem cells (HFSCs). Subsequently, we emphatically investigated the impacts of miRNAs and lncRNAs (cis- and trans- acting) on the genes, indicating that ncRNAs extensively exert negative and positive effects on their expressions. Furthermore, we screened lncRNAs acting as competing endogenous RNAs (ceRNAs) to sponge miRNAs and relief their repressive effects on targeted genes, and constructed related lncRNAs-miRNAs-HOXC8/RSPO1 interactive lines using bioinformatic tools. As a result, XR_310320.3-chi-miR-144-5p-HOXC8, XR_311077.2-novel_624-RSPO1 and others lines appeared, displaying that lncRNAs might serve as ceRNAs to indirectly adjust HFSCs status in hair growth. CONCLUSION: The present study provides an unprecedented inventory of lncRNAs, miRNAs and mRNAs in goat DPCs and DFs. We also exhibit some miRNAs and lncRNAs potentially participate in the modulation of HFSCs activation via delicately adjusting core signatures of DPCs. Our report shines new light on the latent roles and underlying molecular mechanisms of ncRNAs on hair growth.


Assuntos
Cabras/genética , Folículo Piloso/metabolismo , RNA Mensageiro/fisiologia , RNA não Traduzido/fisiologia , Animais , Derme/citologia , Feminino , Fibroblastos/metabolismo , Cabras/metabolismo , Cabelo/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Pele/citologia , Trombospondinas/genética , Transcriptoma
12.
PLoS One ; 14(6): e0218458, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216312

RESUMO

p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by ΔNp73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.


Assuntos
Ectoderma/metabolismo , Pele/metabolismo , Proteína Tumoral p73/genética , Cicatrização/genética , Animais , Proliferação de Células/genética , Dano ao DNA/genética , Ectoderma/crescimento & desenvolvimento , Células Epiteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Queratinócitos/metabolismo , Camundongos , Camundongos Knockout , Análise de Célula Única , Pele/crescimento & desenvolvimento , Pele/lesões , Nicho de Células-Tronco/genética , Transativadores/genética
13.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195626

RESUMO

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.


Assuntos
Vesículas Extracelulares/metabolismo , Folículo Piloso/metabolismo , Pele/metabolismo , Animais , Humanos , Modelos Biológicos , Medicina Regenerativa , Transdução de Sinais
14.
J Cutan Pathol ; 46(11): 844-851, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31161673

RESUMO

Herein, we describe a patient with immunoglobulin G (IgG)-lambda smoldering multiple myeloma with translocation t(4:14) who developed widespread ulcerative horny-like spicules, heralding rapid progression to overt myeloma requiring aggressive chemotherapy and autologous stem cell transplantation. The serum abnormal immunoglobulin in the blood was cryoglobulin, which typically precipitates in the tissues at low temperatures causing inflammation and tissue damage. Histopathological changes, observed in lesions at different evolutionary stages, evidenced columns of horny-like eosinophilic homogeneous material, immunoreactive for IgG lambda, protruding from the dilated and/or distorted follicular openings or acrosyringia and small vessel thrombotic vasculopathy and vasculitis in concert with an inflammatory neutrophilic and lymphocytic reaction. Biochemical investigations on material from a spicule and ulcero-necrotic lesion revealed cryoprecipitates containing IgG-lambda with electrophoretic characteristics identical to those of the serum dysprotein. Our findings suggest that the formation of spicules and development of ulcerative lesions are a part of the same clinical spectrum where the cold-dependent precipitation of the immunogenic dysprotein, both in the skin vessels and hair follicle infundibula, play a major pathogenetic role. Whether this highly characteristic paraneoplastic dermatosis can identify patients with high-risk cytogenetic abnormalities and be incorporated into prognostic models, applicable early on in the course of myeloma, warrants further investigation.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 4/genética , Mieloma Múltiplo , Neoplasias Cutâneas , Mieloma Múltiplo Latente , Translocação Genética , Autoenxertos , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Mieloma Múltiplo Latente/genética , Mieloma Múltiplo Latente/metabolismo , Mieloma Múltiplo Latente/patologia , Mieloma Múltiplo Latente/terapia , Transplante Autólogo
15.
Mol Brain ; 12(1): 31, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943999

RESUMO

Merkel discs, located in skin touch domes and whisker hair follicles, are tactile end organs essential for environmental exploration, social interaction, and tactile discrimination. Recent studies from our group and two others have shown that mechanical stimulation excites Merkel cells via Piezo2 channel activation to subsequently activate sensory neural pathways. We have further shown that mechanical stimulation leads to the release of 5-HT from Merkel cells to synaptically transmit tactile signals to whisker afferent nerves. However, a more recent study using skin touch domes has raised the possibility that Merkel discs are adrenergic synapses. It was proposed that norepinephrine is released from Merkel cells upon mechanical stimulation to subsequently activate ß2 adrenergic receptors on Merkel disc nerve endings leading to nerve impulses. In the present study, we examined effects of norepinephrine and ß2 adrenergic receptor antagonist ICI 118,551 on Merkel disc mechanoreceptors in mouse whisker hair follicles. We show that norepinephrine did not directly induce impulses from Merkel disc mechanoreceptors. Furthermore, we found that ICI 118,551 at 50 µM inhibited voltage-gated Na+ channels and suppressed impulses of Merkel disc mechanoreceptors, but ICI 118,551 at 1 µM had no effects on the impulse. These findings challenge the hypothesis of Merkel discs being adrenergic synapses.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Folículo Piloso/metabolismo , Mecanorreceptores/metabolismo , Células de Merkel/metabolismo , Norepinefrina/farmacologia , Propanolaminas/farmacologia , Sinapses/metabolismo , Vibrissas/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Animais , Folículo Piloso/efeitos dos fármacos , Células de Merkel/efeitos dos fármacos , Sinapses/efeitos dos fármacos
16.
Nat Commun ; 10(1): 1524, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944305

RESUMO

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.


Assuntos
Cabelo/fisiologia , Macrófagos/fisiologia , Regeneração/fisiologia , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Pele/citologia , Pele/metabolismo , Células-Tronco , Estresse Mecânico , Fator de Crescimento Transformador beta
17.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970537

RESUMO

Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes (e.g., wound repair) of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Here we report that growing human hair follicles ex vivo in a defined GAG hydrogel mimicking the dermal matrix strongly promotes sustained cell survival and maintenance of a highly proliferative phenotype in the hair bulb and suprabulbar regions. This significant effect is associated with the activation of WNT/ß-catenin signaling targets (CCDN1, AXIN2) and with the expression of stem cell markers (CK15, CD34) and growth factors implicated in the telogen/anagen transition (TGFß2, FGF10). As a whole, these results point to the dermal GAG matrix as an important component in the regulation of the human hair follicle growth cycle, and to GAG-based hydrogels as potentially relevant modulators of this process both in vitro and in vivo.


Assuntos
Glicosaminoglicanos/farmacologia , Folículo Piloso/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos/métodos , Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosaminoglicanos/química , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Humanos , Hidrogéis/química , Via de Sinalização Wnt
18.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991711

RESUMO

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.


Assuntos
Adiponectina/genética , Cinamatos/farmacologia , Folículo Piloso/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Linhagem Celular , Cinamatos/química , Ésteres/química , Ésteres/farmacologia , Cabelo/citologia , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
19.
Molecules ; 24(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939852

RESUMO

Ancocyanin-rich blackcurrant extract (BCE) has phytoestrogen activity; however, its effect on hair follicles is unknown. Additionally, hair loss is known to occur during menopause in women owing to decreased estrogen secretion. This study examined whether BCE alleviated female pattern hair loss using a rat model. RNA was extracted and analyzed using a microarray and ingenuity pathway analysis. A quantitative polymerase chain reaction revealed that 1 µg/mL BCE altered many genes downstream of beta-estradiol in human hair dermal papilla cells. Additionally, the expression of the hair follicle stem cell marker keratin 19 was greatly enhanced. In a menopause model, ovariectomized rats were fed a diet containing 3% BCE for three months. An analysis of the number of hair shafts revealed that BCE increased the number of hairs by 0.5 hairs/follicular unit. Moreover, immunostaining revealed that the expression of Ki67 also increased by 19%. Furthermore, fluorescent immunostaining showed that the expression of other stem cell markers, including keratin 15, CD34, and keratin 19, was induced in rat hair follicular cells. In conclusion, these findings suggest that BCE has phytoestrogen activity in hair follicles and contributes to the alleviation of hair loss in a menopausal model in rats.


Assuntos
Alopecia/prevenção & controle , Folículo Piloso/efeitos dos fármacos , Ovariectomia , Fitoestrógenos/farmacologia , Extratos Vegetais/farmacologia , Ribes/química , Alopecia/etiologia , Alopecia/patologia , Animais , Feminino , Perfilação da Expressão Gênica , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Ratos , Ratos Sprague-Dawley
20.
J Cutan Pathol ; 46(7): 508-519, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30932205

RESUMO

Hair follicles experience several changes with aging, the most noticeable of which is graying of the hair shaft due to loss of melanin. Additional changes in the diameter and length of the hair have contributed to the concept of senescent alopecia, which is different from androgenetic alopecia according to most. Graying happens in most individuals, although in different grades and starting at different ages. It is related to a decrease in the number and activity of the melanocytes of the hair bulb, which eventually completely disappear from the bulb of the white hair. Residual non-active melanocytes remain in the outer root sheath and in the bulge, which allows for repigmentation of the hair under certain stimuli or conditions.


Assuntos
Envelhecimento/metabolismo , Alopecia/metabolismo , Cor de Cabelo , Folículo Piloso/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Envelhecimento/patologia , Alopecia/patologia , Feminino , Folículo Piloso/patologia , Humanos , Masculino , Melanócitos/patologia
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