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1.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760132

RESUMO

Hair loss, including alopecia, is a common and distressing problem for men and women, and as a result, there is considerable interest in developing treatments that can prevent or reverse hair loss. Dermal papillae closely interact with epidermal cells and play a key role during hair follicle induction and hair morphogenesis. As dermal papilla cells (DPCs) lose their hair­inducing ability in monolayer cultures in vitro, it is difficult to obtain de novo hair follicle structures following DPC transplantation in vivo. The present study aimed to explore culture conditions to maintain DPC characteristics using conditioned media (CM) from the supernatant of cultured HaCaT keratinocyte cells supplemented with other components. Initially, it was observed that during passaging of in vitro monolayer DPC cultures, the Wnt/ß­catenin pathway was repressed, while the TGF­ß/Smad pathway was activated, and that HaCaT cells cultivated in 1% fetal bovine serum had higher levels of expression of Wnt3a and Wnt10b compared with normal keratinocytes. Culturing of high­passage (P7) DPCs in CM from HaCaT cells (HaCaT­CM) actively stimulated cell proliferation and maintained Sox2 and Versican expression levels. Supplementation of HaCaT­CM with SB431542 (SB, a TGF­ß receptor inhibitor), CHIR99021, (CHIR, a GSK3α/ß inhibitor and activator of Wnt signaling) and platelet­derived growth factor (PDGF)­AA further increased the expression levels of Sox2, Versican and alkaline phosphatase (ALP) in P7 DPCs. Three­dimensional culture of P7 DPCs using hanging drop cultures in HaCaT­CM supplemented with SB, CHIR and PDGF­AA resulted in larger cell aggregates and a further significant upregulation of Sox2, ALP and Versican expression levels. Taken together, these findings demonstrated that HaCaT­CM supplemented with SB, CHIR and PDGF­AA may preserve the hair­inducing ability of high­passage DPCs and may therefore be useful in reconstructing new hair follicles in vivo.


Assuntos
Alopecia/genética , Desdiferenciação Celular/efeitos dos fármacos , Derme/crescimento & desenvolvimento , Fator de Crescimento Derivado de Plaquetas/genética , Alopecia/tratamento farmacológico , Alopecia/patologia , Benzamidas/farmacologia , Técnicas de Cultura de Células , Meios de Cultivo Condicionados , Derme/citologia , Dioxóis/farmacologia , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Piridinas/farmacologia , Pirimidinas/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
2.
Methods Mol Biol ; 2202: 51-61, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32857345

RESUMO

Reactive oxygen species (ROS) may severely affect the biochemical viability of most cells. However, ROS may act also as key second messengers regulating important physiological functions in eukaryotic organisms. Of special interest is the potential role of ROS in the regulation of stem cell function and tissue homeostasis and regeneration in adult mammalian tissues. In this context, the hair follicle constitutes an excellent experimental model to study this aspect of ROS biology.Here we present a robust protocol to promote a sustained growth of ex vivo cultured human hair follicles based on the induction of a transient/modulable production of nonlethal endogenous ROS levels in the tissue through a protoporphyrin IX-dependent photodynamic procedure. The light-switchable ROS production activates hair follicle stem cell niches, induces cell proliferation, and maintains the growth/anagen phase for long time. This approach constitutes a complementary experimental tool to study the physiological roles of ROS in human tissues.


Assuntos
Técnicas de Cultura de Células/métodos , Folículo Piloso/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismo , Adulto , Proliferação de Células/fisiologia , Células Cultivadas , Cabelo/fisiologia , Folículo Piloso/metabolismo , Humanos , Nicho de Células-Tronco/fisiologia , Células-Tronco/fisiologia
3.
Gene ; 771: 145343, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33333231

RESUMO

Annexin A1 (ANXA1), a calcium-dependent phospholipid binding protein expressed in animals, plants and microorganisms, participates in various cellular physiological activities. Previous proteomics analysis indicates that the level of ANXA1 in mice dorsal skin changes during hair growth cycle, we speculate that ANXA1 may play an important role in hair follicle (HF) development. Thus, Anxa1 knock-out (KO) and over-expression (OE) mice were constructed to test its function. Our results showed that in addition to the diameter of HF and hair shaft, ANXA1 could participate in hair growth by affecting the density of HF, and the proliferation of hair follicle stem cells (HFSCs). Meanwhile, molecular analysis showed that EGF signaling pathway is involved in the function of ANXA1. The expression of Anxa1 is negatively correlated with the levels of Egf, Notch1, Mkk7, and phosphorylated AKT1 and ERK/2 proteins. The levels of Egf, Notch1, Mkk7 and phosphorylation of AKT1 and ERK/2 increased in Anxa1 KO mice but decreased in Anxa1 OE mice. Taken together, our results suggested that ANXA1 could affect the hair growth by regulating the HFSCs proliferation through EGF signaling pathway.


Assuntos
Anexina A1/genética , Anexina A1/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Animais , Proliferação de Células , Fator de Crescimento Epidérmico/metabolismo , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Folículo Piloso/metabolismo , Camundongos , Fosforilação , Transdução de Sinais
4.
Nat Commun ; 11(1): 5114, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037205

RESUMO

Tissue growth in the adult is an orchestrated process that often requires biological clocks to time stem cell and progenitor activity. Here, we employed the hair follicle, which cycles between growth and regression in a timely-restricted mode, to show that some components of the hair cycle clock reside within the mesenchymal niche of the hair follicle, the dermal papilla (DP), and both Fgf and Wnt signaling pathways interact within the DP to regulate the expression of these components that include Wnt agonists (Rspondins) and antagonists (Dkk2 and Notum). The levels of Wnt agonists and antagonists in the DP are progressively reduced and elevated during the growth phase, respectively. Consequently, Wnt signaling activity in the overlying epithelial progenitor cells decreases, resulting in the induction of the regression phase. Remarkably, DP properties allow Wnt activity in the DP to persist despite the Wnt-inhibiting milieu and consequently synchronize the induction and progression of the regression phase. This study provides insight into the importance of signaling crosstalk in coupling progenitors and their niche to regulate tissue growth.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Via de Sinalização Wnt/fisiologia , Animais , Esterases/genética , Esterases/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos Knockout , Camundongos Mutantes , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Pele/citologia , Trombospondinas/genética , Trombospondinas/metabolismo
6.
Gene ; 758: 144968, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32707304

RESUMO

The hair follicle is an excellent mini-system illustrating the mechanisms governing organogenesis and regeneration. Although the general mechanisms modulating skin and hair follicle development are widely studied in mouse and chicken models, the delicate network regulating skin and hair diversity remains largely unclear. Sheep is an additional model to address the various wool characteristics observed in nature. The coarse and fine wool sheep with diverse fibers were examined to show differences in the primary wool follicle size and skin thickness. The molecular dynamics in skin staged at the primary wool follicle induction between two sheep lines were investigated by RNA-sequencing analyses to generate 1994 differentially expressed genes revealing marker genes for epithelium (6 genes), dermal condensate (38 genes) and dermal fibroblast (58 genes) highly correlated with skin and wool follicle morphological differences. The DEGs were enriched in GO terms represented by epithelial cell migration and differentiation, regulation of hair follicle development and ectodermal placode formation, and KEGG pathways typified by WNT and Hedgehog signaling pathways governing the differences of skin structure. The qPCR detection of 9 genes confirmed the similar expression tendency with RNA-sequencing profiles. This comparative study of coarse and fine wool sheep skin reveals the presence of skin and wool follicle differences at primary wool follicle induction stage, and indicates the potential effectors (APCDD1, FGF20, DKK1, IGFBP3 and SFRP4) regulating the skin compartments during the early morphogenesis of primary wool follicles to shape the variable wool fiber thickness in later developmental stages.


Assuntos
Células Epiteliais/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/fisiologia , Fenômenos Fisiológicos da Pele/genética , Lã/fisiologia , Animais , Proteínas Hedgehog/metabolismo , Simulação de Dinâmica Molecular , Ovinos , Transcriptoma/genética , Via de Sinalização Wnt
7.
Nature ; 582(7812): 399-404, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494013

RESUMO

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor ß (TGFß) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.


Assuntos
Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Organoides/citologia , Células-Tronco Pluripotentes/citologia , Pele/citologia , Animais , Ectoderma/citologia , Feminino , Cabelo/transplante , Cor de Cabelo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/inervação , Folículo Piloso/transplante , Cabeça , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Organoides/crescimento & desenvolvimento , Organoides/inervação , Organoides/transplante , RNA-Seq , Análise de Célula Única , Pele/crescimento & desenvolvimento , Pele/inervação , Transplante de Pele
8.
PLoS One ; 15(4): e0232206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330194

RESUMO

Hair growth is the cyclically regulated process that is characterized by growing phase (anagen), regression phase (catagen) and resting phase (telogen). Hair follicle stem cells (HFSCs) play pivotal role in the control of hair growth cycle. It has been notified that stem cells have the distinguished metabolic signature compared to differentiated cells, such as the preference to glycolysis rather than mitochondrial respiration. Crif1 is a mitochondrial protein that regulates the synthesis and insertion of oxidative phosphorylation (OXPHOS) polypeptides to inner membrane of mitochondria. Several studies demonstrate that tissue-specific knockout of Crif1 leads to mitochondrial dysfunction. In this study, we investigated the effect of mitochondrial dysfunction in terms of Crif1 deficiency on the hair growth cycle of adult mice. We created two kinds of inducible conditional knockout (icKO) mice. In epidermal specific icKO mice (Crif1 K14icKO), hair growth cycle was significantly retarded compared to wild type mice. Similarly, HFSC specific icKO mice (Crif1 K15icKO) showed significant retardation of hair growth cycle in depilation-induced anagen model. Interestingly, flow cytometry revealed that HFSC populations were maintained in Crif1 K15icKO mice. These results suggest that mitochondrial function in HFSCs is important for the progression of hair growth cycle, but not for maintenance of HFSCs.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Animais , Diferenciação Celular/fisiologia , Epiderme/crescimento & desenvolvimento , Epiderme/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Fosforilação Oxidativa , Peptídeos/metabolismo , Células-Tronco/metabolismo
9.
An Bras Dermatol ; 95(3): 278-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32299738

RESUMO

BACKGROUND: The hair follicle is a unique structure, one of the most dynamic structures in mammalians, which can reproduce in every new cycle all the mechanism involved in its fetal development. Although a lot of research has been made about the human hair follicle much less has been discovered about the importance of the cytokeratins (CKs) in its development. OBJECTIVE: Study the immunohistochemical pattern of epithelial CKs during human hair follicle development. METHODS: We performed an immunohistochemical study using fresh post-mortem skin biopsies of human fetuses between 4 and 25 weeks of gestational age to study the expression of cytokeratins (CKs): CK1, CK10, CK13, CK14, CK16 and CK20 during human hair follicle fetal development. STUDY LIMITATIONS: Restrospective study with a good number of makers but with a small population. RESULTS/CONCLUSION: We found that, the CKs were expressed in an intermediate time during follicular development. The epithelial CKs (CK1, CK14, CK10, CK13) and the epithelial CKs with a proliferative character such as CK16 were expressed first, as markers of cellular maturation and follicular keratinization. At a later phase, CK20 was expressed in more developed primitive hair follicles as previously discussed in literature.


Assuntos
Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Queratinas Específicas do Cabelo/análise , Fatores Etários , Anticorpos Monoclonais/análise , Desenvolvimento Fetal , Idade Gestacional , Humanos , Imuno-Histoquímica , Estudos Retrospectivos
10.
Int J Mol Sci ; 21(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218218

RESUMO

Increasing cashmere yield is one of the important goals of cashmere goat breeding. To achieve this goal, we screened the key genes that can improve cashmere performance. In this study, we used the RNA raw datasets of the skin and dermal papilla cells of secondary hair follicle (SHF-DPCs) samples of hair follicle (HF) anagen and telogen of Albas cashmere goats and identified a set of significant differentially expressed genes (DEGs). To explore potential associations between gene sets and SHF growth features and to identify candidate genes, we detected functional enrichment and constructed protein-protein interaction (PPI) networks. Through comprehensive analysis, we selected Thymosin ß4 (Tß4), Rho GTPase activating protein 6 (ARHGAP6), ADAM metallopeptidase with thrombospondin type 1 motif 15, (ADAMTS15), Chordin (CHRD), and SPARC (Osteonectin), cwcv and kazal-like domains proteoglycan 1 (SPOCK1) as candidate genes. Gene set enrichment analysis (GSEA) for these genes revealed Tß4 and ARHGAP6 have a close association with the growth and development of SHF-DPCs. However, the expression of Tß4 in the anagen was higher than that in the telogen, so we finally chose Tß4 as the ultimate research object. Overexpressing Tß4 promoted and silencing Tß4 inhibited the proliferation of SHF-DPCs. These findings suggest that Tß4 can promote the growth and development of SHF-DPCs and indicate that this molecule may be a valuable target for increasing cashmere production.


Assuntos
Proliferação de Células , Folículo Piloso/metabolismo , Timosina/metabolismo , Animais , Células Cultivadas , Ativação Enzimática , Perfilação da Expressão Gênica , Cabras , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Timosina/genética
11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(3): 393-398, 2020 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-32174089

RESUMO

Objective: To explore the research progress of the cell sources and related signaling pathways of the wound-induced hair follicle neogenesis (WIHN) in recent years. Methods: The literature related to WIHN in recent years was reviewed, and the cell sources and molecular mechanism were summarized and discussed. Results: Current research shows that WIHN is a rare regeneration phenomenon in the skin of adult mammals, with multiple cell origins, both hair follicle stem cells and epithelial stem cells around the wound. Its molecular mechanism is complicated, which is regulated by many signaling pathways. Besides, the process is closely related to the immune response, the immunocytes and their related cytokines provide suitable conditions for this process. Conclusion: There are still many unsolved problems on the cellular origins and molecular mechanisms of the WIHN. Further study on the mechanisms will enhance the understanding of adult mammals' hair follicle regeneration and may provide new strategy for functional healing of the human skin.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Regeneração , Pele/lesões , Cicatrização/imunologia , Animais , Citocinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL
13.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947635

RESUMO

Hair loss is a disorder in which the hair falls out from skin areas such as the scalp and the body. Several studies suggest the use of herbal medicine to treat related disorders, including alopecia. Dermal microcirculation is essential for hair maintenance, and an insufficient blood supply can lead to hair follicles (HF) diseases. This work aims to provide an insight into the ethnohistorical records of some nutritional compounds containing flavonoids for their potential beneficial features in repairing or recovering from hair follicle disruption. We started from a query for "alopecia" OR "hair loss" AND "Panax ginseng C.A. Mey." (or other six botanicals) terms included in Pubmed and Web of Sciences articles. The activities of seven common botanicals introduced with diet (Panax ginseng C.A. Mey., Malus pumila Mill cultivar Annurca, Coffea arabica, Allium sativum L., Camellia sinensis (L.) Kuntze, Rosmarinum officinalis L., Capsicum annum L.) are discussed, which are believed to reduce the rate of hair loss or stimulate new hair growth. In this review, we pay our attention on the molecular mechanisms underlying the bioactivity of the aforementioned nutritional compounds in vivo, ex vivo and in vitro studies. There is a need for systematic evaluation of the most commonly used plants to confirm their anti-hair loss power, identify possible mechanisms of action, and recommend their best adoption.


Assuntos
Flavonoides/farmacologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Plantas Comestíveis/química , Plantas Medicinais/química , Animais , Flavonoides/química , Flavonoides/metabolismo , Humanos , Redes e Vias Metabólicas , Estrutura Molecular , Extratos Vegetais/química , Plantas Comestíveis/metabolismo , Plantas Medicinais/metabolismo
14.
J Anim Physiol Anim Nutr (Berl) ; 104(1): 379-384, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31732998

RESUMO

To investigate the effect and molecular mechanism of methionine (Met) on the growth of hair follicles (HFs) in Rex rabbits. A total of 200 weaning Rex rabbits were divided into four groups and fed varying levels of Met-supplemented diets. We measured the HF density on dorsal skin and the Wnt/ß-catenin pathway protein expression level. Meanwhile, whole HFs were isolated from Rex rabbit skins and cultured with Met in vitro to measure hair shaft growth. The relationship between Met and the Wnt/ß-catenin signalling pathway was also characterized by using the Wnt/ß-catenin signalling inhibitor, XAV-939. The results showed that the addition of dietary Met could significantly increase the HF density on dorsal skin (p < .05) and enhance the protein expression level of Wnt10b (p < .05), ß-catenin (p < .05) and DSH (p < .05). Methionine stimulation could also prolong the hair shafts growth in vitro (p < .05). And inhibition of Wnt/ß-catenin signalling using XAV-939 could eliminate this phenomenon. In summary, Met can increase the density of HFs on dorsal skin in vitro and prolong the hair shaft growth of HFs in vivo via the Wnt/ß-catenin signalling pathway.


Assuntos
Folículo Piloso/efeitos dos fármacos , Metionina/farmacologia , Coelhos/crescimento & desenvolvimento , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/genética , beta Catenina/genética
15.
Animal ; 14(6): 1241-1248, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31735193

RESUMO

Melatonin treatment in adult cashmere goats can increase cashmere yield and improve cashmere fibre quality by inducing cashmere growth during cashmere non-growth period, of which time cashmere goats are in the mid and late stages of lactation. However, whether melatonin treatment in adult cashmere goats affects their offspring's growth performance remains unknown. Therefore, the objectives of the current study were to determine the effects of melatonin treatment in adult cashmere goats on cashmere and milk production performance in dams and on hair follicle development and subsequent cashmere production in their offspring. Twenty-four lactating Inner Mongolian Cashmere goat dams (50 ± 2 days in milk, mean ± SD) and their single-born female offspring (50 ± 2 days old, mean ± SD) were randomly assigned to one of two groups supplemented with melatonin implants (MEL; n = 12) or without (CON; n = 12). The melatonin implants were subcutaneously implanted behind the ear at a dose of 2 mg/kg live weight on two occasions - 30 April and 30 June 2016. The results demonstrated that melatonin treatment in adult cashmere goats increased cashmere production and improved cashmere fibre quality as indicated by greater cashmere yield, longer cashmere fibre staple length, finer cashmere fibre diameter and thicker cashmere fibre density. The milk fat content was higher in MEL compared with CON cashmere goats. The daily yields of milk production, milk protein and milk lactose were lower in MEL compared with CON cashmere goats. Serum melatonin concentrations were greater, serum prolactin concentrations were lower and milk melatonin concentrations and yields were greater in MEL compared with CON cashmere goats. With regard to offspring, there were no differences in cashmere yield, fibre staple length, fibre diameter and fibre density at yearling combing, and the primary and secondary hair follicles population and maturation between treatments. In conclusion, melatonin treatment in adult cashmere goats during cashmere non-growth period is a practical and an effective way in cashmere industry as indicated by not only increasing cashmere yield and improving cashmere fibre quality in adult cashmere goat dams but also having no impairment in hair follicle development and the subsequent cashmere production in their single-born offspring.


Assuntos
Cabras/crescimento & desenvolvimento , Folículo Piloso/crescimento & desenvolvimento , Lactação/efeitos dos fármacos , Melatonina/farmacologia , Animais , Suplementos Nutricionais , Feminino , Leite/efeitos dos fármacos , Prolactina/metabolismo
16.
Indian J Dermatol Venereol Leprol ; 86(2): 150-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31823902

RESUMO

Background: Male-type baldness is a common chronic hair loss disorder among males. Male type baldness is characterized by stepwise miniaturization of the hair follicle, due to alteration in the hair cycle dynamics, leading to transformation of the terminal hair follicle into a vellus one. Platelet-rich plasma (PRP) seems to be a new technique which may improve hair regrowth. We planned a randomized, double-blinded placebo control trial to see the efficacy of PRP with and without topical minoxidil and to compare with placebo and standard treatment. Materials and Methods: The study design was a randomized, double-blind placebo control trial. The sample size was calculated, and randomization was done. Patients with male type baldness were allocated into four groups; first group topical minoxidil only, the second group PRP with minoxidil, the third group normal saline (NS), and fourth group PRP only. Interventions were done monthly for 3 months and patients were followed up for the next 2 months. Effects of interventions were assessed by hair density, patient self-assessment, and clinical photography. Results: A total of 80 patients were included. The maximum improvement was found in PRP with minoxidil group. Increase in hair density (in descending order) was PRP with minoxidil group, PRP-alone group, minoxidil-alone group, while a decrease in hair density was found in NS group, after 5 months. The maximum patient satisfaction was found in PRP with minoxidil group followed by (in descending order), PRP-alone group, minoxidil-alone group, and NS group. Limitation: Long-term follow up of patients was not done. Hair counts and hair thickness estimation were not estimated. Conclusion: In our study, we found PRP with topical minoxidil is more effective than PRP alone and topical minoxidil alone.


Assuntos
Alopecia/diagnóstico , Alopecia/terapia , Minoxidil/administração & dosagem , Plasma Rico em Plaquetas , Vasodilatadores/administração & dosagem , Administração Tópica , Adulto , Terapia Combinada/métodos , Método Duplo-Cego , Seguimentos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Humanos , Masculino , Plasma Rico em Plaquetas/fisiologia , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
17.
Clin Exp Dermatol ; 45(3): 309-317, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31556145

RESUMO

BACKGROUND: Consistent with cancer stem cell driven pattern of growth, human basal cell carcinomas (BCCs) demonstrate differentiation along hair follicle (HF) lineages. AIM: To define the pattern of differentiation and therapeutic targets that promote BCC differentiation and therefore BCC cancer stem cell exhaustion. METHODS: An alkaline phosphatase substrate kit was used to determine dermal papilla cells within the BCC stroma. Autonomous HF cycle-dependent gene expression was identified by analysis of the human homologues of a murine gene set (total 2289 genes) that is differentially expressed in hair cycle phases. The findings were validated by quantitative real-time PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)-ß2 stimulation of BCC cancer stem cell colonies. RESULTS: As in the HF, keratin expression in the inner root sheath and matrix in BCC correlated with proliferative index and was tightly regulated, despite the absence of dermal papilla cells. Cross-species microarray analysis comparing human BCC and murine synchronous HF growth cycle datasets revealed 74% concordance with telogen differentiation compared with anagen (23%, P < 0.01) and catagen (49%; P < 0.01). Incomplete anagen differentiation within BCC was characterized by reduced expression of the anagen master regulator DLX3 (-5.5-fold), and increased expression of telogen-associated genes: AEBP1 (2.2-fold), DEFB8 (35.3-fold), MMP3 (106.0-fold) and MMP12 (12.9-fold). Restoration of dermal papilla signals by in vitro addition of TGF-ß2 enhanced anagen differentiation. CONCLUSION: Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators.


Assuntos
Carcinoma Basocelular/patologia , Diferenciação Celular/fisiologia , Folículo Piloso/citologia , Neoplasias Cutâneas/patologia , Animais , Carcinoma Basocelular/fisiopatologia , Transformação Celular Neoplásica , Imunofluorescência , Expressão Gênica , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Queratinas/metabolismo , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Cutâneas/fisiopatologia
18.
Gen Comp Endocrinol ; 286: 113245, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415730

RESUMO

Dihydrotestosterone (DHT) and 17ß-estradiol (E2) are sex hormones that regulate human hair follicle (HF) growth and are produced by peripheral reduction and aromatization of testosterone. However, the expression patterns of DHT and E2 synthesis-related proteins and their receptors in male yak skin during different HF stages (telogen, anagen, and catagen) are unknown. In this study, we found that both 5α-red and androgen receptor (AR) were expressed in epithelial cells and AR was expressed in the dermal papilla. Additionally, the transcription level of 5α-red1 at different HF stages was significantly higher than that of 5α-red2 mRNA at the same stage; 5α-red1 and 5α-red2 proteins peaked during the anagen and telogen periods of HF, respectively. However, AR protein was only expressed in the skin during the anagen phase of HF. Aromatase and estrogen receptors (ERα and ERß) were expressed in cutaneous epithelial cells, whereas ERα and ERß were expressed in the dermal papilla; the transcription level of ERα in HFs at each stage was much higher than that of ERß. From the catagen to telogen phase, aromatase protein expression was down-regulated, while ERα protein expression was up-regulated. Based on our results, we speculate that 5α-red1 is essential for the synthesis of DHT in male yak skin epithelial cells and promotes the growth of HFs through AR. E2 synthesized by male yak skin epithelial cells may inhibit the growth of male yak skin HFs by ERα. These results provide a foundation for further study on the mechanism of hormone-regulated male yak skin HFs.


Assuntos
Antígeno 12E7/metabolismo , Di-Hidrotestosterona/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Animais , Bovinos , Folículo Piloso/metabolismo , Masculino
19.
Genomics ; 112(1): 332-345, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30779940

RESUMO

Guard hair and cashmere undercoat are developed from primary and secondary hair follicle, respectively. Little is known about the gene expression differences between primary and secondary hair follicle cycling. In this study, we obtained RNA-seq data from cashmere and milk goats grown at four different seasons. We studied the differentially expressed genes (DEGs) during the yearly hair follicle cycling, and between cashmere and milk goats. WNT, NOTCH, MAPK, BMP, TGFß and Hedgehog signaling pathways were involved in hair follicle cycling in both cashmere and milk goat. However, Milk goat DEGs between different months were significantly more than cashmere goat DEGs, with the largest difference being identified in December. Some expression dynamics were confirmed by quantitative PCR and western blot, and immunohistochemistry. This study offers new information sources related to hair follicle cycling in milk and cashmere goats, which could be applicable to improve the wool production and quality.


Assuntos
Cabras/genética , Folículo Piloso/metabolismo , Transcriptoma , Animais , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Genômica , Cabras/metabolismo , Folículo Piloso/crescimento & desenvolvimento , RNA-Seq , Estações do Ano , Proteínas da Superfamília de TGF-beta/genética , Proteínas da Superfamília de TGF-beta/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
20.
Gene ; 733: 144242, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31743770

RESUMO

OBJECTIVE: To investigate fibroblast growth factor 21 (Fgf21) alterations that may affect hair growth and the underlying molecular mechanisms by constructing Fgf21 global knockout (KO) mice using microinjection-mediated CRISPR/Cas9. RESULTS: Following genomic DNA sequencing, we identified 18 mice carrying Ffg21 mutations among the total 63 offspring mice obtained by injecting 340 embryos, which yielded a mutation rate of 28.6 percent. Of these 18 mice, three had both alleles knocked out and 15 were monoallelic KO mice. Compared with the wild-type (WT) mice, the phenotypic analysis showed that the litter size of Fgf21 KO mice significantly reduced (p < 0.05), but physiological indexes of the birth weight, gender rate, body weight (0-8 week) and body weight of adult male and female were no significant difference (p > 0.05). Compared to WT mice, physiological anatomy indicated that the morphological characters of vital organs in Fgf21 KO mice were normal. Depilation experiments demonstrated that compared to the WT mice, the hair regrowth speed was reduced in the Fgf21 KO mice. The number of hair shafts in these mice considerably decreased, as indicated by the tissue sample analyses. Real-time quantitative PCR showed that Erk and Akt expression in the KO mice was significantly decreased (P < 0.05), whereas western blotting demonstrated that the expression of Erk and Akt proteins and their phosphorylation levels in KO mice decreased at different rates (P < 0.05). CONCLUSIONS: Fgf21 was shown to affect hair follicle development and growth cycle, which may be associated with Pi3k/Akt and Mapk/Erk signaling pathways.


Assuntos
Fatores de Crescimento de Fibroblastos/genética , Folículo Piloso/crescimento & desenvolvimento , Cabelo/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Engenharia Genética/métodos , Folículo Piloso/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
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