Melanocyte development
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Vitiligo is the most common depigmentation disorder of the skin. Currently, its therapy focuses on the halting of the immune response and stimulation of the regenerative processes, leading to the restoration of normal melanocyte function. Platelet-rich plasma (PRP) represents a safe and cheap regenerative therapy option, as it delivers a wide spectrum of native growth factors, cytokines and other bioactive molecules. The aim of this study was to develop a simple delivery system to prolong the effects of the bioactive molecules released from platelets. The surface of electrospun and centrifugally spun poly-ε-caprolactone (PCL) fibrous scaffolds was functionalized with various concentrations of platelets; the influence of the morphology of the scaffolds and the concentration of the released platelet-derived bioactive molecules on melanocytes, was then assessed. An almost two-fold increase in the amount of the released bioactive molecules was detected on the centrifugally spun vs. electrospun scaffolds, and a sustained 14-day release of the bioactive molecules was demonstrated. A strong concentration-dependent response of melanocyte to the bioactive molecules was observed; higher concentrations of bioactive molecules resulted in improved metabolic activity and proliferation of melanocytes. This simple system improves melanocyte viability, offers on-site preparation and is suitable for prolonged topical PRP administration.
- MeSH
- lékové transportní systémy * metody MeSH
- lidé MeSH
- melanocyty MeSH
- plazma bohatá na destičky * MeSH
- vitiligo terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The c-myb proto-oncogene and its oncogenic derivative v-mybAMV encode transcriptional regulators engaged in the commitment of hematopoietic cells. While the c-Myb protein is important for the formation and differentiation of various progenitors, the v-MybAMV oncoprotein induces in chicks a progression and transformation of the single (monoblastic) cell lineage. Here we present the first evidence of cell fate-directing abilities of c-Myb and v-MybAMV proteins in avian neural crest (NC), where both proteins determine melanocytogenesis. The increased concentration of c-Myb induces progression into dendritic melanocytes and differentiation. The v-myb oncogene converts essentially all NC cells into melanocytes and causes their transformation. Both Myb proteins activate in NC cells expression of the c-kit gene and stem cell factor c-Kit signaling--one of the essential pathways in melanocyte development. These observations suggest that the c-myb-c-kit pathway represents a common regulatory scheme for both hematopoietic and neural progenitors and establishes a novel experimental model for studies of melanocytogenesis and melanocyte transformation.
- MeSH
- buněčná diferenciace MeSH
- crista neuralis cytologie metabolismus MeSH
- DNA primery genetika MeSH
- financování organizované MeSH
- geny myb MeSH
- kuřecí embryo MeSH
- melanocyty cytologie metabolismus MeSH
- onkogenní proteiny v-myb genetika metabolismus MeSH
- protoonkogenní proteiny c-kit genetika metabolismus MeSH
- protoonkogenní proteiny c-myb genetika metabolismus MeSH
- růstový faktor kmenových buněk genetika metabolismus MeSH
- sekvence nukleotidů MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
To test the hypothesis of whether cellular blue nevi (CBN) may originate from "ordinary" compound and dermal nevi, a total of 275 melanocytic nevi including 59 CBN, 34 ordinary blue nevi, 87 combined nevi (including 43 so-called clonal nevi), 35 deep penetrating nevi, and 60 ordinary compound and dermal nevi (30 of each) were studied for the presence of so-called ball-in-mitts and microalveolar structures. A ball-in-mitts structure was defined as a single centrally placed melanocyte with a round to oval nucleus (the "ball" cell) and a clear, dusty, or pigmented cytoplasm encircled by a single dendritic cell (the "mitt" cell) with an oval to spindle-shaped nucleus and slender bipolar processes containing melanin and surrounding at least one fourth of the ball's diameter. A microalveolar structure was defined as a group of 2 to 10 centrally placed melanocytes with round to oval nuclei and clear, dusty, or pigmented cytoplasm (balls) surrounded by one or more cells (mitts) with spindle-shaped nuclei and slender bipolar processes containing melanin. Microscopically, ball-in-mitt and microalveolar structures were detected in all types of nevi studied, with the highest incidence in combined nevi (82%), CBN (76%), and ordinary "nonblue" nevi (73%). In CBN, ball-in-mitts and microalveolar structures tended to be located in the deeper portion of the lesions, whereas in ordinary nonblue nevi, they were most often found superficially, just below the epidermis; in clonal nevi, these structures were often confined to the "clonal" parts. Immunohistochemically, ball-in-mitts and microalveolar structures were positive for HMB45. Ultrastructurally, the balls tended to have round to oval nuclei, whereas the mitts possessed oval, elongated to spindled nuclei. Melanosomes were found in various stages in the cells of both structures. The cytoplasm of the mitts typically formed elongated polar processes, sometimes with club-like widenings at the ends, completely or partially encircling the balls. In the microalveolar structures, the adjacent cells forming the mitts surrounded the ball cells like a chain. Our study suggests that some or even most cases of CBN may evolve from ordinary nonblue nevi. This process may involve several steps and is probably reflected by the appearances of combined nevi, deep penetrating nevi, and CBN. These nevi often show a morphological overlap, and ball-in-mitts and microalveolar structures found in various stages of their development seem to greatly account for this overlap.
- MeSH
- antigeny nádorové MeSH
- buněčné jádro patologie ultrastruktura MeSH
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanocyty patologie MeSH
- mladiství MeSH
- modrý névus etiologie metabolismus patologie MeSH
- nádorové proteiny metabolismus MeSH
- nádory kůže etiologie metabolismus patologie MeSH
- névus patologie MeSH
- pigmentový névus etiologie metabolismus patologie MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- imunohistochemie MeSH
- lidé MeSH
- meduloblastom genetika MeSH
- nádorový supresorový protein p53 MeSH
- neuroektodermové nádory genetika MeSH
- pilotní projekty MeSH
- polymerázová řetězová reakce MeSH
- prognóza MeSH
- regulace genové exprese u nádorů genetika imunologie MeSH
- sekvence nukleotidů MeSH
- Check Tag
- lidé MeSH
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
- MeSH
- autoprotilátky * MeSH
- ghrelin imunologie MeSH
- inzulin imunologie MeSH
- leptin imunologie MeSH
- lidé MeSH
- melanocyty stimulující hormony imunologie MeSH
- neuropeptid Y imunologie MeSH
- poruchy příjmu potravy imunologie mikrobiologie MeSH
- střevní mikroflóra imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Melanin production is the primary mechanism protecting human skin against the UV light-induced damage. The polymeric compound melanin is synthesized within melanocytes in the specialized subcellular organelles, termed melanosomes, which are then transferred to surrounding keratinocytes. The genes for melanin synthesis and deposition are coordinately expressed in melanocytes. The transcription factor MITF, which has been reported to activate more than 25 genes in pigment cells, has emerged as an essential regulator not only for melanocyte development, proliferation and survival, but also for the expression of enzymes and structural proteins ensuring the production of melanin. MITF is a transcriptional activator of several genes which encode melanosome-localized proteins involved both in melanin synthesis and in melanosome biogenesis and transport, including genes whose mutations are associated with human oculocutaneous and ocular forms of albinism. Here, we outline the mechanisms of transcriptional regulation of genes associated with the biosynthesis of melanin in melanocytes and melanoma cells. MITF is crucial in this process, while several other factors seem to have only an auxiliary role to play under specific circumstances.
- MeSH
- biologické modely MeSH
- fyziologický stres MeSH
- lidé MeSH
- melaniny biosyntéza MeSH
- melanocyty cytologie fyziologie MeSH
- melanom genetika patofyziologie MeSH
- melanozomy fyziologie MeSH
- pigmentace kůže genetika fyziologie MeSH
- promotorové oblasti (genetika) MeSH
- sekvence nukleotidů MeSH
- trans-aktivátory genetika fyziologie MeSH
- transkripční faktor spojený s mikroftalmií genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.
- MeSH
- buněčná diferenciace * MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory kůže * patologie vrozené MeSH
- pigmentový névus * patologie vrozené MeSH
- předškolní dítě MeSH
- Schwannovy buňky * patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. RESULTS: We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. CONCLUSION: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.
- MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- lidé MeSH
- melanom krevní zásobení metabolismus MeSH
- nádorové biomarkery analýza MeSH
- nádory kůže krevní zásobení metabolismus MeSH
- patologická angiogeneze metabolismus MeSH
- pigmentový névus krevní zásobení metabolismus MeSH
- proteiny intermediálních filament biosyntéza MeSH
- proteiny nervové tkáně biosyntéza MeSH
- Check Tag
- lidé MeSH
Nevocelulární nevus může vzniknout dvojí cestou: 1. po chronické solární radiaci kůže, kdy je porušena homeostáza barierových lipidů a nejen keratinocyt, ale také melanocyt je odsouzen k apoptóze. 2. Stejně může být apoptózou postižen melanocyt během fylogenetické cesty z neurální lišty do epidermis, když prochází „nepřátelským“ územím dermis. Apoptózu však může pozastavit enzymatický proces, který vede k anoikis, a ta dovede ohrožený melanocyt k nové proliferaci. Tak se vyvíjí nevocelulární nevus.
Nevocellular nevus can develop by two mechanisms: 1. after the chronic solar irradiation of the skin which impairs barrier lipids' homeostais and keratinocytes together with melanocytes undergo apoptosis; 2. Apoptosis can arise in melanocytes during phylogenetic development from the neural crest to epidermis when it migrates through the „enemy” territory of dermis. Apoptosis can be thus stopped by enzymatic process which results in anoikis and the endangered melanocyte would further proliferate. The later is the path of nevocellular nevi.
2mg/kg melanotan II (MTII, administered i.p.), a cyclic peptide analog of alpha-melanocyte stimulating hormone, at a single dose increased grooming in naive rats placed in an unfamiliar open-field device without changing locomotion or rearing. Male rats exposed to restraint/immobilization stress (IS) for 1h on three consecutive days displayed increased grooming after the second stressor exposure, compared to pre-stress levels. MTII, administered to the rats after IS, enhanced the grooming response compared both to the pre- and post-stress values. The increase was greatest after the first dose and declined over the following two applications. As to the locomotion of rats in the entire experimental space, IS reduced the distance moved only after the first two stressor exposures; MTII did not influence these alterations. Locomotion in the central part of arena was not reduced by the stressor or by MTII, on the contrary, there was an increase in both groups after the third intervention. The only observed change in rearing was an increase in the MTII group after the third restraint exposure. Thus, MTII selectively increased grooming without markedly affecting the spatio-temporal structure of locomotor behavior in the open-field. The decline of MTII enhanced grooming over the three test days may be interpreted in terms of adaptation to the stressor and of the developing tolerance to the peptide.
- MeSH
- alfa-MSH analogy a deriváty farmakologie MeSH
- chování zvířat MeSH
- cyklické peptidy farmakologie MeSH
- fyzické omezení MeSH
- krysa rodu rattus MeSH
- melanokortiny antagonisté a inhibitory MeSH
- pátrací chování fyziologie účinky léků MeSH
- péče o zevnějšek u zvířat fyziologie účinky léků MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH