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1.
Science ; 367(6474): 161-166, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31857493

RESUMO

Tissue homeostasis requires the balance of growth by cell production and regression through cell loss. In the hair cycle, during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cell reservoir and trigger new growth. Here, we identify the dermal sheath that lines the follicle as the key driver of tissue regression and niche relocation through the smooth muscle contractile machinery that generates centripetal constriction force. We reveal that the calcium-calmodulin-myosin light chain kinase pathway controls sheath contraction. When this pathway is blocked, sheath contraction is inhibited, impeding follicle regression and niche relocation. Thus, our study identifies the dermal sheath as smooth muscle that drives follicle regression for reuniting niche and stem cells in order to regenerate tissue structure during homeostasis.


Assuntos
Derme/fisiologia , Folículo Piloso/fisiologia , Músculo Liso/fisiologia , Regeneração , Nicho de Células-Tronco/fisiologia , Agrecanas/genética , Animais , Humanos , Camundongos , Camundongos Mutantes , Contração Muscular
2.
Biol Pharm Bull ; 42(9): 1446-1449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474706

RESUMO

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.


Assuntos
Flavonoides/farmacologia , Cor de Cabelo , Folículo Piloso/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Animais , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/fisiologia , Flavonoides/química , Folículo Piloso/fisiologia , Luteolina/química , Luteolina/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/fisiologia , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Relação Estrutura-Atividade
3.
BMC Cancer ; 19(1): 723, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331318

RESUMO

BACKGROUND: Copy number gain of the D-3-phosphoglycerate dehydrogenase (PHGDH) gene, which encodes the first enzyme in serine biosynthesis, is found in some human cancers including a subset of melanomas. METHODS: In order to study the effect of increased PHGDH expression in tissues in vivo, we generated mice harboring a PHGDHtetO allele that allows tissue-specific, doxycycline-inducible PHGDH expression, and we analyzed the phenotype of mice with a ubiquitous increase in PHGDH expression. RESULTS: Tissues and cells derived from PHGDHtetO mice exhibit increased serine biosynthesis. Histological examination of skin tissue from PHGDHtetO mice reveals the presence of melanin granules in early anagen hair follicles, despite the fact that melanin synthesis is closely coupled to the hair follicle cycle and does not normally begin until later in the cycle. This phenotype occurs in the absence of any global change in hair follicle cycle timing. The aberrant presence of melanin early in the hair follicle cycle following PHGDH expression is also accompanied by increased melanocyte abundance in early anagen skin. CONCLUSIONS: These data suggest increased PHGDH expression impacts normal melanocyte biology, but PHGDH expression alone is not sufficient to cause cancer.


Assuntos
Expressão Gênica , Melaninas/metabolismo , Fosfoglicerato Desidrogenase/genética , Alelos , Animais , Linhagem Celular , Doxiciclina/farmacologia , Folículo Piloso/fisiologia , Humanos , Melanócitos/metabolismo , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Serina/biossíntese , Pele/metabolismo , Neoplasias Cutâneas/metabolismo
4.
Elife ; 82019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343406

RESUMO

Skin vasculature cross-talking with hair follicle stem cells (HFSCs) is poorly understood. Skin vasculature undergoes dramatic remodeling during adult mouse hair cycle. Specifically, a horizontal plexus under the secondary hair germ (HPuHG) transiently neighbors the HFSC activation zone during the quiescence phase (telogen). Increased density of HPuHG can be induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1) in adult mice, and is accompanied by prolonged HFSC quiescence and by delayed entry and progression into the hair growth phase (anagen). Suggestively, skin vasculature produces BMP4, a well-established HFSC quiescence-inducing factor, thus contributing to a proliferation-inhibitory environment near the HFSC. Conversely, the HFSC activator Runx1 regulates secreted proteins with previously demonstrated roles in vasculature remodeling. We suggest a working model in which coordinated remodeling and molecular cross-talking of the adult epithelial and endothelial skin compartments modulate timing of HFSC activation from quiescence for proper tissue homeostasis of adult skin.


Assuntos
Diferenciação Celular , Folículo Piloso/fisiologia , Cabelo/crescimento & desenvolvimento , Fenômenos Fisiológicos da Pele , Células-Tronco/fisiologia , Remodelação Vascular , Animais , Homeostase , Camundongos
5.
Nat Commun ; 10(1): 2811, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243280

RESUMO

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.


Assuntos
Folículo Piloso/fisiologia , RNA de Cadeia Dupla/fisiologia , Regeneração/fisiologia , Receptor 3 Toll-Like/metabolismo , Tretinoína/metabolismo , Animais , Benzoatos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Interleucina-6/administração & dosagem , Interleucina-6/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno , Estilbenos/farmacologia , Cicatrização
6.
Med Hypotheses ; 128: 83-85, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31203916

RESUMO

Higher risk of rapid progression in alopecia or male pattern baldness was observed in men who had family history. This could result from accumulation of DHT in hair follicles. Hair follicles on frontal region are more vulnerable to DHT. With development of minimal invasive hair transplantation surgery, hair follicles transplantation could be performed from frontal or occipital region to frontal region. However, limited hair follicles remained a problem. With development of technology of vitrification, we suggested extracting hair follicles from frontal region without affecting the appearance and preserving them with vitrification when the patient was young. When alopecia progressively developed, these extracted hair follicles would increase the donor number of hair follicles used for transplantation, which could extend longer dense hair appearance.


Assuntos
Folículo Piloso/fisiologia , Folículo Piloso/transplante , Cabelo/transplante , Vitrificação , Alopecia/terapia , Androgênios/metabolismo , Cabeça , Humanos , Masculino , Modelos Teóricos , Doadores de Tecidos
7.
Cells ; 8(6)2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216669

RESUMO

There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.


Assuntos
Derme/metabolismo , Derme/patologia , Cicatrização/fisiologia , Animais , Cicatriz/metabolismo , Cicatriz/patologia , Derme/fisiologia , Matriz Extracelular , Fibroblastos/fisiologia , Folículo Piloso/fisiologia , Humanos , Queloide/patologia , Miofibroblastos/fisiologia , Regeneração/fisiologia , Pele/metabolismo , Pele/patologia , Fenômenos Fisiológicos da Pele , Pele Artificial
8.
Neurosci Lett ; 705: 14-19, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30936034

RESUMO

Loss of the sense of touch or numbness in fingertips and toes is one of the earliest sensory dysfunctions in patients receiving chemotherapy with anti-cancer drugs such as vincristine. However, mechanisms underlying this chemotherapy-induced sensory dysfunction is poorly understood. Whisker hair follicles are tactile organs in non-primate mammals which are functionally equivalent to human fingertips. Here we used mouse whisker hair follicles as a model system to explore how vincristine treatment induces the loss of the sense of touch. We show that chronic treatment of mice with vincristine impaired in vivo whisker tactile behavioral responses. In vitro electrophysiological recordings made from whisker hair follicle afferent nerves showed that mechanically evoked whisker afferent impulses were significantly reduced following vincristine treatment. Furthermore, patch-clamp recordings from Merkel cells of whisker hair follicles revealed a significant reduction of mechanically activated currents via Piezo2 channels in Merkel cells. Collectively, our results suggest that Piezo2 channel dysfunction in Merkel cells contribute to the loss of the sense of touch following the chemotherapy treatment regimen with vincristine.


Assuntos
Folículo Piloso/efeitos dos fármacos , Canais Iônicos/metabolismo , Células de Merkel/efeitos dos fármacos , Tato/efeitos dos fármacos , Vincristina/efeitos adversos , Animais , Folículo Piloso/fisiologia , Técnicas In Vitro , Células de Merkel/fisiologia , Camundongos , Tato/fisiologia , Vibrissas/fisiologia
9.
PLoS Genet ; 15(4): e1008034, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017901

RESUMO

Melanocyte stem cells (McSCs) are the undifferentiated melanocytic cells of the mammalian hair follicle (HF) responsible for recurrent generation of a large number of differentiated melanocytes during each HF cycle. HF McSCs reside in both the CD34+ bulge/lower permanent portion (LPP) and the CD34- secondary hair germ (SHG) regions of the HF during telogen. Using Dct-H2BGFP mice, we separate bulge/LPP and SHG McSCs using FACS with GFP and anti-CD34 to show that these two subsets of McSCs are functionally distinct. Genome-wide expression profiling results support the distinct nature of these populations, with CD34- McSCs exhibiting higher expression of melanocyte differentiation genes and with CD34+ McSCs demonstrating a profile more consistent with a neural crest stem cell. In culture and in vivo, CD34- McSCs regenerate pigmentation more efficiently whereas CD34+ McSCs selectively exhibit the ability to myelinate neurons. CD34+ McSCs, and their counterparts in human skin, may be useful for myelinating neurons in vivo, leading to new therapeutic opportunities for demyelinating diseases and traumatic nerve injury.


Assuntos
Antígenos CD34/metabolismo , Melanócitos/imunologia , Melanócitos/fisiologia , Células-Tronco/imunologia , Células-Tronco/fisiologia , Animais , Diferenciação Celular , Células Cultivadas , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Cor de Cabelo/fisiologia , Folículo Piloso/citologia , Folículo Piloso/fisiologia , Melanócitos/classificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Nus , Camundongos Transgênicos , Proteína Básica da Mielina/deficiência , Proteína Básica da Mielina/genética , Crista Neural/citologia , Crista Neural/imunologia , Crista Neural/fisiologia , Pigmentação/fisiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Regeneração/fisiologia , Células-Tronco/classificação
10.
Nanoscale ; 11(13): 6315-6333, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30882821

RESUMO

Due to the complexity of the skin tissue structure, the regeneration of the entire skin, including skin appendages such as hair follicles, is a big challenge. In addition, skin trauma is often accompanied by bacterial infections that delay the wound healing. Therefore, developing wound dressings, which promote hair follicle regeneration and inhibit bacterial infection in the wound healing process, is of great clinical significance. In this study, Zn doped hollow mesoporous silica nanospheres (HMZS) were synthesized by a sol-gel method and a novel wound healing dressing was prepared by incorporation of drug ciprofloxacin hydrochloride (CiH)-loaded Zn containing mesoporous silica nanospheres (CiH-HMZS) into polycaprolactone (PCL) electrospun fibers. The CiH-HMZS/P nano-composite electrospun fibers exhibit the ability to promote angiogenesis and skin regeneration by releasing Si ions, and the activity to enhance hair follicle regeneration and inhibit bacterial growth by releasing zinc ions and achieve the synergistic antibacterial effect with both Zn ions and CiH in low concentrations. Thus, the CiH-HMZS/P nano-composite membrane is a promising multi-functional wound healing material for inhibiting bacterial growth in infected wounds and enhancing skin wound healing including hair follicle regeneration.


Assuntos
Antibacterianos/química , Folículo Piloso/fisiologia , Nanocompostos/química , Poliésteres/química , Dióxido de Silício/química , Cicatrização/efeitos dos fármacos , Zinco/química , Animais , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ciprofloxacino/química , Ciprofloxacino/farmacologia , Portadores de Fármacos/química , Escherichia coli/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanocompostos/uso terapêutico , Nanocompostos/toxicidade , Neovascularização Fisiológica/efeitos dos fármacos , Porosidade , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos
12.
BMC Genomics ; 20(1): 140, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770723

RESUMO

BACKGROUND: Hair fibre length is an important economic trait of rabbits in fur production. However, molecular mechanisms regulating rabbit hair growth have remained elusive. RESULTS: Here we aimed to characterise the skin traits and gene expression profiles of short-hair and long-hair rabbits by histological and transcriptome analyses. Haematoxylin-eosin staining was performed to observe the histological structure of the skin of short-hair and long-hair rabbits. Compared to that in short-hair rabbits, a significantly longer anagen phase was observed in long-hair rabbits. In addition, by RNA sequencing, we identified 951 genes that were expressed at significantly different levels in the skin of short-hair and long-hair rabbits. Nine significantly differentially expressed genes were validated by quantitative real-time polymerase chain reaction. A gene ontology analysis revealed that epidermis development, hair follicle development, and lipid metabolic process were significantly enriched. Further, we identified potential functional genes regulating follicle development, lipid metabolic, and apoptosis as well as important pathways including extracellular matrix-receptor interaction and basal cell carcinoma pathway. CONCLUSIONS: The present study provides transcriptome evidence for the differences in hair growth between short-hair and long-hair rabbits and reveals that lipid metabolism and apoptosis might constitute major factors contributing to hair length.


Assuntos
Cabelo/anatomia & histologia , Cabelo/crescimento & desenvolvimento , Coelhos/anatomia & histologia , Coelhos/genética , Pele/anatomia & histologia , Transcriptoma , Processamento Alternativo , Animais , Apoptose/genética , Epiderme/crescimento & desenvolvimento , Epiderme/metabolismo , Feminino , Folículo Piloso/anatomia & histologia , Folículo Piloso/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Metabolismo dos Lipídeos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Análise de Sequência de RNA , Fenômenos Fisiológicos da Pele
13.
Int J Low Extrem Wounds ; 18(1): 42-55, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30616449

RESUMO

Full-thickness skin wounds are common accidents. Although healing can be achieved by treatments like autologous skin grafts, donor site morbidity is hardly evitable. In this article, we provide compelling evidence demonstrating that artificial dermal template (ADT)-treated wound healing is achieved by regrowth of skin epidermis as well as adnexa without skin grafts by use of rodent models. First, by fixating a chamber to the wound edge, we confirmed that wound healing was achieved by regeneration instead of contracture. We found highly proliferative cells in adnexa in the newly formed skin. In the distal edge of newly formed skin, we identified immature hair follicles at early developing stages, suggesting they were newly regenerated. Second, we observed that the Lgr5-positive hair follicle stem cells contributed to formation of new hair follicles through a lineage tracing model. Also, Lgr6-positive cells were enriched in distal edge of newly developed skin. Finally, WNT signaling pathway mediators were highly expressed in the new skin epidermis and adnexa, implying a potential role of WNT signaling during ADT treatment-stimulated skin regrowth. Taken together, our findings demonstrated that full skin regrowth can be induced by ADT treatment alone, thus arguing for its wide clinical application in skin wound treatment.


Assuntos
Transplante de Pele/métodos , Pele Artificial , Pele/lesões , Cicatrização/fisiologia , Ferimentos e Lesões/cirurgia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Folículo Piloso/fisiologia , Imuno-Histoquímica , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Regeneração/fisiologia , Sensibilidade e Especificidade , Ferimentos e Lesões/diagnóstico
14.
Orbit ; 38(5): 383-386, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30482080

RESUMO

Purpose: To describe and evaluate the eyelash transplantation with strip composite eyebrow graft to improve eyelid anatomy in tarsoconjunctival flap eyelid reconstruction procedure. Methods: Twenty two patients with eyelid tumors managed by local excision and reconstruction using tarsoconjunctival flap reconstruction procedure were included. Eyelash graft was performed during flap division by harvesting a graft from the eyebrow and creating a recipient pocket in the receptor eyelid. Patients had a 1-year follow up. Eyelash orientation and follicle survival rate were recorded. Demographic variables were analyzed with descriptive statistics. For eyelash follicles survival rate assessment, we evaluated the number of follicles found in the first postoperative day with the follicles found at the end of the study using the Wilcoxon signed rank test. P < 0.05 was considered statistically significant. Results: All eyelash grafts showed a good follicle orientation and no cases of eyelashes misdirection toward the eyeball were reported. No statistical differences (p > 0.05) were found in Wilcoxon signed rank test when comparing the number of follicles present at the first postoperative day and the number of follicles present at the 12th postoperative month, meaning that the vast majority of follicles survived at the end of the study. Graft ischemia, necrosis or infection were not observed. Conclusions: Tarsoconjunctival flap is an outstanding option for eyelid reconstruction and eyelash transplantation with an eyebrow composite graft is an excellent procedure to enhance and recreate a normal eyelid.


Assuntos
Túnica Conjuntiva/cirurgia , Sobrancelhas/transplante , Pestanas/transplante , Pálpebras/cirurgia , Cabelo/transplante , Procedimentos Cirúrgicos Reconstrutivos , Retalhos Cirúrgicos , Idoso , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Feminino , Folículo Piloso/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Sutura
15.
Mol Med Rep ; 19(1): 549-554, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30483790

RESUMO

Nestin, a type-VI intermediate filament protein, serves as a marker for neural stem cells, and is also known to be expressed in follicle stem cells. Hair follicles go through repeated cycles of anagen (growth), catagen (regression) and telogen (quiescence) throughout the life of mammals following morphogenesis. In the present study it was demonstrated that in mice, the maturation of hair follicles includes the period between morphogenesis and the first anagen (4 weeks of age). Skin samples from Nestin­green fluorescent protein (GFP)+ mice at different hair follicle stages were collected, and immunostaining for Nestin and Ki67 was performed. It was identified that during morphogenesis, Nestin­GFP expression was rarely detected and it gradually increased during maturation (0­4 weeks) in hair follicle dermal cells. In mature hair follicle dermal cells, Nestin and the proliferation marker Ki67 were highly expressed in anagen, while during telogen, they were markedly decreased. Additionally, lineage tracing data demonstrated that peri­follicular Nestin+ cells during morphogenesis differentiated into cluster of differentiation 31+ cells.


Assuntos
Folículo Piloso/fisiologia , Nestina/genética , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Proteínas de Fluorescência Verde/genética , Antígeno Ki-67/genética , Camundongos , Morfogênese/genética , Morfogênese/fisiologia , Pele/fisiopatologia , Células-Tronco/fisiologia
16.
J Anim Physiol Anim Nutr (Berl) ; 103(2): 501-508, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30593693

RESUMO

The aim of this study was conducted to investigate the effect of heat stress on the hair follicle population and related signalling pathways in rex rabbits. Forty-eight rabbits were randomly divided into two groups: one group in a high ambient environment (32 ± 2°C, heat stress) and the other group with normal temperature (20 ± 2°C, control). The results show that heat stress decreased the body weight gain and feed conversion rate, rabbit hair length and hair follicle density (p < 0.05). Besides, heat stress suppressed the gene expression of noggin, insulin-like growth factor 1 (IGF-1) and IGF-1 receptor and protein expression of phosphorylated mechanistic target of rapamycin (mTOR) in rabbit skin (p < 0.05), while stimulated significantly the gene expression of bone morphogenetic protein 2 (BMP2) and BMP4 (p < 0.05). Heat exposure did not alter significantly the gene expression of alkaline phosphatase, versican and hepatocyte growth factor compared with the control (p > 0.05). In conclusion, noggin-BMP, IGF-1 and mTOR signalling pathways may be associated with the process of heat stress-repressing hair follicle development.


Assuntos
Folículo Piloso/fisiologia , Resposta ao Choque Térmico , Coelhos/fisiologia , Animais , Regulação da Expressão Gênica , Fenômenos Fisiológicos da Pele
17.
Life Sci ; 220: 194-200, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30584899

RESUMO

Lysophosphatidic acid (LPA) is the simplest phospholipid found in nature. LPA is mainly biosynthesized in tissues and cells by autotoxin and PA-PLA1α/PA-PLA1ß and is degraded by lipid phosphate phosphatases (LPPs). It is an important component of biofilm, an extracellular signal transmitter and intracellular second messenger. After targeting to endothelial differentiation gene (Edg) family LPA receptors (LPA1, LPA2, LPA3) and non-Edg family LPA receptors (LPA4, LPA5, LPA6), LPA mediates physiological and pathological processes such as embryonic development, angiogenesis, tumor progression, fibrogenesis, wound healing, ischemia/reperfusion injury, and inflammatory reactions. These processes are induced through signaling pathways including mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3K)/Akt, protein kinase C (PKC)-GSK3ß-ß-catenin, Rho, Stat, and hypoxia-inducible factor 1-alpha (HIF-1α). LPA is involved in multiple physiological and pathological processes in the skin. It not only regulates skin function but also plays an important role in hair follicle development, skin wound healing, pruritus, skin tumors, and scleroderma. Pharmacological inhibition of LPA synthesis or antagonization of LPA receptors is a new strategy for the treatment of various skin disorders. This review focuses on the current understanding of the pathophysiologic role of LPA in the skin.


Assuntos
Lisofosfolipídeos/metabolismo , Lisofosfolipídeos/fisiologia , Pele/metabolismo , Animais , Folículo Piloso/fisiologia , Humanos , Lisofosfolipídeos/farmacologia , Receptores de Ácidos Lisofosfatídicos/metabolismo , Receptores de Ácidos Lisofosfatídicos/fisiologia , Transdução de Sinais/efeitos dos fármacos , Pele/patologia , Cicatrização/fisiologia
18.
Exp Mol Med ; 50(12): 160, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30523246

RESUMO

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.


Assuntos
Alopecia/terapia , Biguanidas/uso terapêutico , Folículo Piloso/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Animais , Biguanidas/síntese química , Diferenciação Celular , Reprogramação Celular , Metabolismo Energético , Glicólise , Regeneração Tecidual Guiada , Folículo Piloso/efeitos dos fármacos , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células MCF-7 , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
19.
J Hum Evol ; 125: 99-105, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30502901

RESUMO

Humans differ in many respects from other primates, but perhaps no derived human feature is more striking than our naked skin. Long purported to be adaptive, humans' unique external appearance is characterized by changes in both the patterning of hair follicles and eccrine sweat glands, producing decreased hair cover and increased sweat gland density. Despite the conspicuousness of these features and their potential evolutionary importance, there is a lack of clarity regarding how they evolved within the primate lineage. We thus collected and quantified the density of hair follicles and eccrine sweat glands from five regions of the skin in three species of primates: macaque, chimpanzee and human. Although human hair cover is greatly attenuated relative to that of our close relatives, we find that humans have a chimpanzee-like hair density that is significantly lower than that of macaques. In contrast, eccrine gland density is on average 10-fold higher in humans compared to chimpanzees and macaques, whose density is strikingly similar. Our findings suggest that a decrease in hair density in the ancestors of humans and apes was followed by an increase in eccrine gland density and a reduction in fur cover in humans. This work answers long-standing questions about the traits that make human skin unique and substantiates a model in which the evolution of expanded eccrine gland density was exclusive to the human lineage.


Assuntos
Glândulas Écrinas/fisiologia , Folículo Piloso/fisiologia , Macaca mulatta/fisiologia , Pan troglodytes/fisiologia , Animais , Evolução Biológica , Humanos
20.
J. optom. (Internet) ; 11(4): 211-222, oct.-dic. 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-178500

RESUMO

The primary role of eyelashes is to protect and maintain the health of the lid margin. However, the mechanisms to fulfill this role are not fully understood. Unraveling these mechanisms will stand to greatly improve the efficiency of eye care professionals’ interventions in anomalies of the eyelashes. The aim of this article is to provide a review on eyelashes including highlights and new avenues for research; the biology of both the lash and its follicle; the pathophysiology and management of lash anomalies by eye care professionals; and the effect of iatrogenic factors on lashes. Using the database of Ovid MEDLINE, we reviewed studies specifically directed on human/mammalian eyelashes and key articles on current trends in scalp hair methodologies that can be applicable to lash research. The eyelash morphology, pigmentation and growth rate have been documented using techniques ranging from lash imaging to follicle immunohistochemistry. Furthermore, studies have demonstrated that the lash follicle is sensitive to many factors of the external environment, a variety of systemic/topical medications and cosmetics. Recently, aerodynamic studies using a mammalian eye model confirmed that an optimal lash length was needed so that eyelashes serve a protective role in reducing the number of particles that can reach the eye. Despite recent advances in lash research, studies are still scarce, due to the limited availability of the human lid for sampling. This review brings awareness that further research is needed with respect to eyelashes and will hopefully reduce the gap with scalp hair research


La función principal de las pestañas es proteger y mantener la salud del margen palpebral. Sin embargo, los mecanismos de desempeño de esta función no se comprenden plenamente. Desentrañar estos mecanismos ayudará a mejorar la eficiencia de las intervenciones de los profesionales de cuidados oculares en cuanto a las anomalías de las pestañas. El objetivo de este artículo es aportar una revisión sobre las pestañas, incluyendo los aspectos más destacados y las nuevas aportaciones para la investigación, la biología de la pestaña y su folículo, la patofisiología y tratamiento de las anomalías de las pestañas por parte de los profesionales de cuidados oculares, y el efecto de los factores iatrogénicos sobre las pestañas. Utilizando la base de datos de Ovid MEDLINE, revisamos los estudios específicamente dirigidos a las pestañas humanas/de mamíferos, así como los artículos clave sobre las tendencias actuales en cuanto a las metodologías del cuero cabelludo, que pueden aplicarse a la investigación sobre las pestañas. Se han documentado la morfología de las pestañas, así como su pigmentación y tasa de crecimiento, utilizando técnicas que oscilan entre la imagen de las pestañas y la inmunohistoquímica del folículo. Además, los estudios han demostrado que el folículo de la pestaña es sensible a diversos factores del entorno externo, diversas medicaciones sistémicas/tópicas y cosméticos. Recientemente, los estudios aerodinámicos que han utilizando un modelo de ojo de mamífero, han confirmado que se precisaba una longitud de pestañas óptima para que éstas ejercieran su función protectora a la hora de reducir el número de partículas que pueden acceder al ojo. A pesar de los avances recientes de la investigación sobre las pestañas, los estudios son aún escasos, debido a la disponibilidad limitada de párpado humano para muestreo. Esta revisión sirve de concienciación acerca de la necesidad de investigación futura con respecto a las pestañas, que reducirá presumiblemente la brecha existente con respecto a la investigación sobre el cuero cabelludo


Assuntos
Humanos , Pestanas/anatomia & histologia , Pestanas/fisiologia , Doenças Palpebrais/fisiopatologia , Doenças do Cabelo/fisiopatologia , Folículo Piloso/anatomia & histologia , Folículo Piloso/fisiologia , Envelhecimento/fisiologia , Doença Iatrogênica
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