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1.
Int J Nanomedicine ; 14: 8409-8419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695374

RESUMO

Introduction: Hair growth-promoting herbal extract mixtures (4HGF) exhibits significant anti-inflammatory activities relevant to promoting hair growth; however, its efficacy in patients with hair loss has been limited majorly due to its low penetration ability into hair follicles. Herein, we prepared hydrogels via dropwise addition of poly(γ-glutamic acid) (PGA) solution containing 4HGF into chitosan (CS) solution, resulting in quick formation of ~400 nm-sized hydrogel particles through electrostatic interaction-derived ionic gelation with over 50% encapsulation efficiency of 4HGF (PGA-4HGF). Methods: The size and morphology of PGA-4HGF were characterized by TEM, SEM, and dynamic light scattering analyses. Encapsulation efficiency and loading capacity of 4HGF within PGA-4HGF, as well as in vitro release profiles were determined by simply measuring the characteristic absorbance of 4HGF. Penetrating efficiency of PGA-4HGF was evaluated by tracking the respective fluorescence through model porcine skin with confocal laser microscope system. By treating PGA-4HGF on telogenic mice and dermal papilla cells (DPCs), we evaluated the size of hair bulbs in mice, as well as morphological changes in DPCs. Results: Negligible and sustained release of entrapped 4HGF from the hydrogel nanoparticles were observed under acidic and physiological pH conditions, respectively, which is quite advantageous to control their release and prolong their hair growth-promoting effect. The hydrogel nanoparticles were penetrable through the porcine skin after incubation with or without shaking. After treating telogenic mice and DPCs with PGA-4HGF, we detected enlargement of hair bulbs and remarkable shape changes, respectively, thereby showing its potential in induction of hair growth. Conclusion: These results suggest that the hydrogel nanoparticle formulation developed in this study can be employed as a potential approach for the preservation of hair growth-promoting compounds, their delivery of into hair follicles, and enhancing hair growth.


Assuntos
Quitosana/química , Fermentação , Folículo Piloso/crescimento & desenvolvimento , Hidrogéis/química , Nanopartículas/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ácido Poliglutâmico/análogos & derivados , Animais , Compostos de Bifenilo/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Depuradores de Radicais Livres/farmacologia , Folículo Piloso/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Tamanho da Partícula , Picratos/química , Ácido Poliglutâmico/química , Temperatura Ambiente
2.
Int J Nanomedicine ; 14: 7921-7931, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632009

RESUMO

Purpose: We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice. Methods: N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively. Results: The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD. Conclusion: We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).


Assuntos
Sistemas de Liberação de Medicamentos , Cabelo/crescimento & desenvolvimento , Minoxidil/administração & dosagem , Minoxidil/farmacologia , Nanopartículas/química , Animais , Cabelo/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Minoxidil/sangue , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Solubilidade , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
J Microbiol Biotechnol ; 29(11): 1830-1840, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31601058

RESUMO

Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a threedimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of ß-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/ ß-catenin signaling pathways.


Assuntos
Benzofuranos/farmacologia , Derme/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Derme/citologia , Células HEK293 , Folículo Piloso/crescimento & desenvolvimento , Humanos , Queratinócitos/efeitos dos fármacos , Monoterpenos/farmacologia , Fosforilação/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
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
5.
EMBO J ; 38(19): e101688, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475747

RESUMO

Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell-dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue-level, thus provide insight into their functional contribution to skin regeneration.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Vasos Linfáticos/metabolismo , Regeneração , Fenômenos Fisiológicos da Pele , Animais , Ciclo Celular , Camundongos , Nicho de Células-Tronco
7.
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
8.
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
9.
J Pharmacol Exp Ther ; 370(2): 299-307, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152005

RESUMO

Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature-activated Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome, characterized by skin diseases and alopecia, indicating an important role for TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference, and pharmacological approaches. We found that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining, and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B and short-hairpin RNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle-related skin diseases.


Assuntos
Morte Celular/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Canais de Cátion TRPV/metabolismo , Temperatura Ambiente , Animais , Ácidos Cafeicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Células HEK293 , Folículo Piloso/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
10.
Cells ; 8(5)2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100937

RESUMO

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (ß-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).


Assuntos
Alopecia/terapia , Folículo Piloso/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Medicina Regenerativa/métodos , Transplante de Células-Tronco , Células-Tronco/metabolismo , Via de Sinalização Wnt , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Humanos , Plasma Rico em Plaquetas , Engenharia Tecidual/métodos
11.
Life Sci ; 229: 210-218, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102746

RESUMO

AIMS: Hair follicles play a critical role in the process of hair growth. The dermal papilla cells (DPCs) are an important component in the hair follicle regeneration and growth. This study investigated the effects of ginsenoside Rb1 on the growth of cultured mink hair follicles and DPCs. MAIN METHODS: The mink hair follicles were treated with ginsenoside Rb1 for 9 days and their lengths were measured every three days. Real-time PCR was used to determine the mRNA expression of vascularization endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGF-R2) and TGF-ß1. In addition, the levels of proteins were detected by western blot. Cell proliferation was determined by immunofluorescence staining of proliferation marker Ki-67 and cell cycle analysis was performed on flow cytometry. Moreover, cell migration was evaluated by wound healing assay. KEY FINDINGS: Ginsenoside Rb1 promoted the growth of hair follicles, and proliferation and migration of DPCs. Ginsenoside Rb1 improved the expression levels of VEGFA and VEGF-R2, while attenuated the TGF-ß1 expression both in hair follicles and DPCs. Furthermore, ginsenoside Rb1 facilitated the activation of PI3K/AKT/GSK-3ß signaling pathway in hair follicles and DPCs. SIGNIFICANCE: The results reveals a crucial role of PI3K/AKT/GSK-3ß signaling pathway in ginsenoside Rb1-induced growth of hair follicles and DPCs.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/genética , Folículo Piloso/efeitos dos fármacos , Masculino , Vison , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Cicatrização
12.
PLoS One ; 14(5): e0216003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042749

RESUMO

Alopecia is a clinical condition caused by excessive hair loss which may result in baldness, the causes of which still remain elusive. Conditioned media (CM) from stem cells shows promise in regenerative medicine. Our aim was to evaluate the potential CM of dental pulp stem cells obtained from human deciduous teeth (SHED-CM) to stimulate hair growth under in vitro and in vivo conditions. SHED and hair follicle stem cells (HFSCs) (n = 3) were cultured in media combinations; i) STK2, ii) DMEM-KO+10% FBS, iii) STK2+2% FBS and profiled for the presence of positive hair growth-regulatory paracrine factors; SDF-1, HGF, VEGF-A, PDGF-BB and negative hair growth-regulatory paracrine factors; IL-1α, IL-1ß, TGF-ß, bFGF, TNF-α, and BDNF. The potential of CM from both cell sources to stimulate hair growth was evaluated based on the paracrine profile and measured dynamics of hair growth under in vitro conditions. The administration of CM media to telogen-staged synchronized 7-week old C3H/HeN female mice was carried out to study the potential of the CM to stimulate hair growth in vivo. SHED and HFSCs cultured in STK2 based media showed a shorter population doubling time, higher viability and better maintenance of MSC characteristics in comparison to cells cultured in DMEM-KO media. STK2 based CM contained only two negative hair growth-regulatory factors; TNF-α, IL-1 while DMEM-KO CM contained all negative hair growth-regulatory factors. The in vitro study confirmed that treatment with STK2 based media CM from passage 3 SHED and HFSCs resulted in a significantly higher number of anagen-staged hair follicles (p<0.05) and a significantly lower number of telogen-staged hair follicles (p<0.05). Administration of SHED-CM to C3H/HeN mice resulted in a significantly faster stimulation of hair growth in comparison to HFSC-CM (p<0.05), while the duration taken for complete hair coverage was similar for both CM sources. Thus, SHED-CM carries the potential to stimulate hair growth which can be used as a treatment tool for alopecia.


Assuntos
Alopecia/terapia , Meios de Cultivo Condicionados/farmacologia , Cabelo/efeitos dos fármacos , Células-Tronco Adultas/metabolismo , Animais , Polpa Dentária/patologia , Feminino , Cabelo/crescimento & desenvolvimento , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C3H
13.
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
14.
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
15.
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
16.
Arch Dermatol Res ; 311(5): 411-420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006055

RESUMO

Hair loss affects men and women of all ages. Dermal papilla (DP) plays a crucial role in regulating the growth and cycling of hair follicles. Lactoferrin (LF) exhibits a wide range of biological functions, including antimicrobial activity and growth regulation. However, its effect on DP and its role in hair growth remain unknown. In this study, we found that bovine LF (bLF) promoted the proliferation of DP cells and enhanced the phosphorylation of Erk and Akt. The bLF-mediated proliferation was significantly blocked by the Erk phosphorylation inhibitor PD98059 or the Akt phosphorylation inhibitor LY294002. Moreover, biotin-labeled bLF could bind to DP cells, and the binding was independent of lipoprotein receptor-related protein 1, a known LF receptor. Importantly, bLF stimulated hair growth in both young and aged mice. Moreover, we also found that bLF significantly induced the expression of Wnt signaling-related proteins, including Wnt3a, Wnt7a, Lef1, and ß-catenin. The bLF-mediated DP cell proliferation could be significantly reversed by the Wnt pathway inhibitor XAV939. Our findings suggest that bLF promotes hair growth in mice and stimulates proliferation of DP cells through Erk/Akt and Wnt signaling pathways. This study highlights a great potential of the use of bLF in developing drugs to treat hair loss.


Assuntos
Alopecia/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Lactoferrina/farmacologia , Alopecia/patologia , Animais , Células Cultivadas , Feminino , Folículo Piloso/crescimento & desenvolvimento , Lactoferrina/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Animais , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Via de Sinalização Wnt/efeitos dos fármacos
17.
Biosci Biotechnol Biochem ; 83(6): 1045-1061, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30935300

RESUMO

MicroRNAs (miRNAs) regulate the development and growth cycle of hair follicles (HFs). The molecular mechanism by which miRNAs determine the development of HFs in the sheep foetus remains elusive. In this study, the expression profiles of miRNAs at 11 development periods (45, 55, 65, 75, 85, 95, 105, 115, 125, 135 and 145 d) in sheep foetus skin were analysed by high-throughput sequencing and bioinformatics analysis. A total of 72 conserved miRNAs, 44 novel miRNAs and 32 known miRNAs were significantly differentially expressed. qRT-PCR results for 18 miRNAs were consistent with the sequencing data. 85 d of foetal development was the starting point for secondary hair follicle (SF) development according to tissue morphology and cluster analysis. In SF development, the prolactin signalling pathway and platelet activation played important roles, and 10 miRNAs were potential candidate miRNAs in SF initiation.


Assuntos
Desenvolvimento Fetal/genética , Perfilação da Expressão Gênica , Folículo Piloso/crescimento & desenvolvimento , MicroRNAs/genética , Ovinos/embriologia , Animais , Biologia Computacional , Regulação para Baixo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Ativação Plaquetária , Prolactina/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Análise de Sequência de RNA/métodos , Transdução de Sinais , Regulação para Cima ,
18.
Genes (Basel) ; 10(4)2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987022

RESUMO

Animal growth and development are regulated by long non-coding RNAs (lncRNAs). However, the functions of lncRNAs in regulating cashmere fineness are poorly understood. To identify the key lncRNAs that are related to cashmere fineness in skin, we have collected skin samples of Liaoning cashmere goats (LCG) and Inner Mongolia cashmere goats (MCG) in the anagen phase, and have performed RNA sequencing (RNA-seq) approach on these samples. The high-throughput sequencing and bioinformatics analyses identified 437 novel lncRNAs, including 93 differentially expressed lncRNAs. We also identified 3,084 differentially expressed messenger RNAs (mRNAs) out of 27,947 mRNAs. Gene ontology (GO) analyses of lncRNAs and target genes in cis show a predominant enrichment of targets that are related to intermediate filament and intermediate filament cytoskeleton. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, sphingolipid metabolism is a significant pathway for lncRNA targets. In addition, this is the first report to reveal the possible lncRNA-mRNA regulatory network for cashmere fineness in cashmere goats. We also found that lncRNA XLOC_008679 and its target gene, KRT35, may be related to cashmere fineness in the anagen phase. The characterization and expression analyses of lncRNAs will facilitate future studies on the potential value of fiber development in LCG.


Assuntos
Cabras/genética , Folículo Piloso/química , RNA Longo não Codificante/genética , Pele/metabolismo , Animais , Biologia Computacional , Redes Reguladoras de Genes/genética , Cabras/crescimento & desenvolvimento , Folículo Piloso/crescimento & desenvolvimento , Sequenciamento de Nucleotídeos em Larga Escala , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , RNA Mensageiro/genética , Pele/crescimento & desenvolvimento
19.
Dermatol Surg ; 45(12): 1649-1659, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30865019

RESUMO

BACKGROUND: Appropriate storage of human hair follicle (HF) grafts during follicular unit excision (FUE) is crucial toward successful hair shaft implantation. Several commercial storage solutions are currently used to ensure ex vivo maintenance of follicular grafts viability and trichogenicity. However, quantitative experimental evidence demonstrating molecular changes in HF cells associated with the usage of different storage solutions is largely missing. OBJECTIVE: To identify gene expression changes in HF cells caused by ex vivo storage of hair grafts in different preservation conditions. METHODS: The authors performed gene expression analysis in dermal papilla (DP) isolated from HF stored under different temperatures and solutions. The expression signature of key genes controlling hair growth and cycling, apoptosis, inflammation, and senescence was assessed for (1) chilled versus room temperature (RT) and (2) DP cell medium, saline, Hypothermosol, platelet-rich plasma, and ATPv-supplemented saline. RESULTS: The authors found chilled versus RT to prevent inflammatory cytokine signaling. Under chilled conditions, ATPv-supplemented saline was the best condition to preserve the expression of the trichogenic genes HEY1 and LEF1. CONCLUSION: Data disclose DP gene expression analysis as a useful methodology to ascertain the efficacy of preserving solutions and elucidate about the best currently available option for FUE clinical practice.


Assuntos
Células-Tronco Adultas/metabolismo , Alopecia/terapia , Folículo Piloso/crescimento & desenvolvimento , Soluções para Preservação de Órgãos/farmacologia , Organogênese/efeitos dos fármacos , Trifosfato de Adenosina/farmacologia , Adolescente , Adulto , Células-Tronco Adultas/efeitos dos fármacos , Aloenxertos/efeitos dos fármacos , Aloenxertos/crescimento & desenvolvimento , Aloenxertos/transplante , Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/transplante , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos/química , Temperatura Ambiente , Coleta de Tecidos e Órgãos/métodos , Adulto Jovem
20.
Gene ; 698: 19-26, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30825596

RESUMO

Adult stem cells are self-renewing populations that originate from embryonic progenitor cells during organogenesis and retain multipotency to support tissue and organ regeneration throughout the lifetime of an organism. The hair follicle (HF) is a small organ that is ideal for studying the biology and regulation of adult stem cells. A distinct, permanent pool of adult stem cells is located in the HF bulge region. Most methods used to isolate hair follicle stem cells (HFSCs) begin with mouse or human follicles. Here, we describe two methods of isolating HFSCs from newborn Yangtze River Delta White Goats. A suitable method was found. The cell viability and expression of HFSC marker proteins differed in the two methods. CD49f-positive (integrin alpha 6) HFSCs were sorted by fluorescence activated flow cytometry. Sorted HFSCs can be used in various in vivo grafting models and are useful as an in vitro model to study multipotency, quiescence and activation.


Assuntos
Células-Tronco Adultas/citologia , Técnicas de Cultura de Células/métodos , Folículo Piloso/metabolismo , Células-Tronco Adultas/fisiologia , Animais , Proliferação de Células , Sobrevivência Celular , Cabras/genética , Folículo Piloso/crescimento & desenvolvimento , Organogênese/genética , Cultura Primária de Células/métodos , Regeneração/genética
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