MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6001 - 6001

Published: May 26, 2022

Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. Although it has been studied extensively in cutaneous melanoma, the role MITF uveal melanoma (UM) not explored much detail. We review literature about normal melanocytes, UM. In regulates development, melanin synthesis, survival. The expression profile behaviour MITF-expressing cells suggest that promotes local proliferation inhibits invasion, inflammation, epithelial-to-mesenchymal (EMT) transition. Loss leads to increased invasion inflammation more prevalent malignant cells. Cutaneous switch between MITF-high MITF-low states different phases tumour UM, loss associated with BAP1 protein expression, which a marker poor prognosis. These data indicate dual for benign melanocytic

Language: Английский

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Cytotoxicity of ZnO nanoparticles in human melanocyte cells in the presence or absence of UV radiation: A preliminary comparative study with TiO2 nanoparticles

Toxicology in Vitro, Journal Year: 2025, Volume and Issue: 106, P. 106051 - 106051

Published: March 12, 2025

Language: Английский

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3D melanoma spheroid model for the development of positronium biomarkers

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 11, 2023

It was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium utilizes properties of atoms, which are built from electrons and positrons produced body during PET examinations. We hypothesized would sensitive vitro discrimination tumor-like three-dimensional structures (spheroids) melanoma cell lines different activities biological properties. The lifetime ortho-positronium (o-Ps) evaluated spheroids two (WM266-4 WM115) differing stage malignancy. Additionally, we considered parameters such as number, spheroid size malignancy evaluate their relationship o-Ps lifetime. demonstrate pilot results measurement extracellular matrix-free spheroids. With statistical significance standard deviations, higher degree rate proliferation neoplastic cells, shorter ortho-positronium. In particular, observed following indications encouraging further research: (i) WM266-4 characterized a showed than WM115 lower growth rate. (ii) Both decrease after generation on day 8 compared 4 culture, mean longer formed cells those regardless age. this study revealed is promising biomarker applied assessment

Language: Английский

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Concentration‐dependent stimulation of melanin production as well as melanocyte and keratinocyte proliferation by melatonin in human eyelid epidermis

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 32(5), P. 684 - 693

Published: Jan. 5, 2023

Abstract It remains unclear how the multifunctional indoleamine neurohormone, melatonin, alters melanin production and melanocytes within intact human epidermis under physiologically relevant conditions. In current pilot study, we aimed to clarify this in long‐term organ‐cultured, full‐thickness eyelid skin, selected for its clinically recognized sensitivity pigmentation‐modulatory hormones. Warthin‐Starry histochemistry showed that 100 μM melatonin significantly increased epidermal content melanocyte dendricity after 6 days of organ culture, even though tyrosinase activity situ was inhibited, as assessed by quantitative immunohistomorphometry. While higher dose tested here (200 μM) did not change melanization, but again inhibited activity, it number proliferation both gp100 + keratinocytes well protein expression premelanosomal marker, gp100, ex vivo. Contrary most previous studies, these skin culture results suggest application exerts overall stimulatory, dose‐dependent effects on pigmentary unit which appear surprisingly tyrosinase‐independent. provocative preliminary findings require further work‐up independent confirmation, they encourage one systematically explore whether prolonged therapy can (re‐)stimulate melanogenesis increase pool/activity hypopigmented lesions.

Language: Английский

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The Skin–Brain Axis: From UV and Pigmentation to Behaviour Modulation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6199 - 6199

Published: June 4, 2024

The skin–brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson’s disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly indirectly regulate behaviour. Conversely, CNS-driven neural hormonal responses have demonstrated pigmentation, e.g., under stress. Additionally, due the shared neuroectodermal origins of melanocytes neurons CNS, certain CNS diseases be linked pigmentation-related changes common regulators, MC1R variations. Furthermore, HPA analogue connects endocrine system, thereby allowing index possible abnormalities visibly. In this review, insight is provided into pigment production neuromelanin synthesis brain recent findings are summarised on how signalling skin, with particular focus interconnected central nervous system. Thus, review supply better understanding mechanism associations health disease.

Language: Английский

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Targeting the Complexity of In Vitro Skin Models: A Review of Cutting-Edge Developments

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(12), P. 2650 - 2670

Published: Aug. 10, 2024

Skin in vitro models offer much promise for research, testing drugs, cosmetics, and medical devices, reducing animal extensive clinical trials. There are several approaches to mimicking human skin behavior, ranging from simple cell monolayer complex organotypic bioengineered 3-dimensional models. Some have been approved preclinical studies pharmaceuticals, chemicals. However, development of physiologically reliable remains its infancy. This review reports on advances study homeostasis, aging, disease. The generation that accurately reproduce all layers (epidermis, dermis, subcutis), including appendages such as sweat glands (SGs), hair follicles, or arrector pili muscle, represents a significant hurdle the field tissue engineering. we still far full cellular structural complexity living (Antoni et al., 2015Antoni D. Burckel H. Josset E. Noel G. Three-dimensional culture: breakthrough vivo.Int J Mol Sci. 2015; 16: 5517-5527Crossref PubMed Scopus (699) Google Scholar; Sanabria-de la Torre 2020Sanabria-de R. Fernández-González A. Quiñones-Vico M.I. Montero-Vilchez T. Arias-Santiago S. Bioengineered intended model Pharmacosmetics, disease environmental impact analysis.Biomedicines. 2020; 8: 464Crossref (17) Sutterby 2022Sutterby Thurgood P. Baratchi Khoshmanesh K. Pirogova Evaluation studying effects external stressors stimuli developing treatment modalities.View. 2022; 320210012Crossref (18) Scholar). demand innovative effective (3D) engineered equivalents has increased not only improving purposes grafts but also essential (patho)physiological investigations, unravel underlying mechanisms disorders well assessing effectiveness potential toxicity active substances cosmetic pharmaceutical research (Olejnik 2022Olejnik Semba J.A. Kulpa Dańczak-Pazdrowska Rybka J.D. Gornowicz-Porowska J. 3D bioprinting related research: recent achievements application perspectives.ACS Synth Biol. 11: 26-38Crossref (40) Salameh 2021Salameh Tissot N. Cache Lima Suzuki I. Marinho P.A. al.A perfusable vascularized full-thickness topical systemic applications.Biofabrication. 2021; 13035042Crossref (30) Current aim replicate critical characteristics, barrier function, elasticity, immune response, blood flow, technical biological issues limit true functional (Klicks 2017Klicks von Molitor Ertongur-Fauth Rudolf Hafner M. In three-dimensional their applications.J Cell Biotechnol. 2017; 3: 21-39Crossref evolution substitutes paralleled technological resulted with varying degrees complexity. Although is linear, main drive innovation lies physiologic relevance (Figure 1). simplest approach 2-dimensional (2D) culture primary keratinocytes fibroblasts. do cell–cell cell–matrix communication organization skin, they very useful drug screening; cytotoxicity assays; molecular diseases cancer (Duval 2017Duval Grover Han L.H. Mou Y. Pegoraro A.F. Fredberg al.Modeling physiological events 2D vs. culture.Physiology (Bethesda). 32: 266-277Crossref (1158) Hofmann 2023Hofmann Fink Pignet A.L. Schwarz Schellnegger Nischwitz S.P. al.Human wound healing disorders.Biomedicines. 2023; 1056Crossref Moon 2021Moon Kim D.H. Shin J.U. response skin.Yonsei Med 62: 969-980Crossref (0) Stanton 2022Stanton D.N. Ganguli-Indra Indra A.K. Karande efficacy disease: last 10 years.Pharmaceutics. 14: 319Crossref (5) Incorporation extracellular matrix (ECM) components into provided cells important cues native environment, promoting more representative growth, proliferation, function resembling some conditions vivo Langhans, 2018Langhans S.A. discovery repositioning.Front Pharmacol. 2018; 9: 6Crossref (1000) Sarkiri 2019Sarkiri Fox S.C. Fratila-Apachitei L.E. Zadpoor A.A. modeling.Int 2019; 20: 1407Crossref (24) Valdoz 2021Valdoz J.C. Johnson B.C. Jacobs D.J. Franks N.A. Dodson E.L. Sanders C. al.The ECM: scaffold, question.Int 2212690Crossref (60) systems includes organoids 1), simplified system which grow 3D-well chemically defined microenvironment—composed ECM media—to form self-organized clusters differentiate distinct types mimic structure organ (Corrò 2020Corrò Novellasdemunt L. Li V.S.W. A brief history organoids.Am Physiol Physiol. 319: C151-C165Crossref Hofer Lutolf, 2021Hofer Lutolf M.P. Engineering organoids.Nat Rev Mater. 6: 402-420Crossref (524) 2020bKim Koo B.K. Knoblich Human organoids: biology medicine.Nat 21: 571-584Crossref Whereas recapitulate different internal organs gut (Taelman 2022Taelman Diaz Guiu intestinal challenge.Front Dev 10854740Crossref (31) Scholar), lung (Matkovic Leko 2023Matkovic Schneider R.T. Thimraj T.A. Schrode Beitler Liu H.Y. distal organoid interstitial disease, viral infection development.Nat Protoc. 18: 2283-2312Crossref brain (Eichmüller Knoblich, 2022Eichmüller O.L. cerebral - new tool neurology research.Nat Neurol. 661-680Crossref (21) bladder (Minoli 2023Minoli Cantore Hanhart Kiener Fedrizzi La Manna F. al.Bladder stages therapy response.Nat Commun. 2214Crossref tumors (Xu 2022Xu Jiao Wu Tumor applications modeling potentials precision medicine.J Hematol Oncol. 15: 58Crossref (69) traditional consist 2 dermo–epidermal formed by fibroblasts embedded an gel cultured top gel, generated insert's porous membrane allow epidermal keratinization (Gangatirkar 2007Gangatirkar Paquet-Fifield Rossi Kaur Establishment cultures using neonatal cells.Nat 2007; 2: 178-186Crossref (124) These (HSEs) well-established available market (Hayden 2003Hayden P.J. Ayehunie Jackson G.R. Kupfer-Lamore Last T.J. al.In equivalent testing.in: Alternative toxicological methods. CRC Press, Boca Raton2003: 229-248Google Suhail 2019Suhail Sardashti Jaiswal Rudraiah Misra Kumbar S.G. Engineered product evaluation therapeutic applications.Biotechnol 14e1900022Crossref (46) Presently, there range commercially HSEs offering source screening, tests, sensitivity tests (Table Several patients, animal-based, ex assays used identify potentially irritant chemicals compatible high-throughput screening required industry. This, along legislative move toward nonanimal (European Regulation 1223/2009 United States Federal Food, Drug, Cosmetic Act, 2022), prompted commercial regulatory toxicology, validated epithelial-only methods corrosion irritation adopted Organisation Economic Co-operation Development (Test Guidelines 431 439, respectively) (Kandárová 2006Kandárová Liebsch Schmidt Genschow Traue Spielmann al.Assessment SkinEthic reconstructed common protocol evaluated ECVAM validation study.Altern Lab Anim. 2006; 34: 393-406Crossref (52) 2007Spielmann Hoffmann Botham Fentem J.H. Eskes international acute irritation: report validity Episkin EpiDerm Integrity Function Test.Altern 35: 559-601Crossref (184) based metabolic activity, provide indirect measure viability, 50% threshold set acceptable chemical safety levels. More sophisticated (KeratinoSens [Andreas 2011Andreas Caroline B. Leslie Frank Kimberly Allison intra- inter-laboratory reproducibility predictivity KeratinoSens assay predict sensitizers vitro: results ring-study five laboratories.Toxicol Vitro. 2011; 25: 733-744Crossref (98) Emter 2010Emter Ellis Natsch Performance novel keratinocyte-based reporter line screen vitro.Toxicol Appl 2010; 245: 281-290Crossref (269) Scholar] LuSens [Ramirez 2014Ramirez Mehling Kolle S.N. Wruck C.J. Teubner W. Eltze al.LuSens: keratinocyte ARE gene use integrated strategies sensitization hazard identification.Toxicol 2014; 28: 1482-1497Crossref (104) Scholar]) utilize luciferase basis induced activation transcription factor, nuclear factor erythroid 2. these architecture permeability yet be translated systems. number altered expression profiles known irritants, SENS-IS being currently most developed (Cottrez 2015Cottrez Boitel Auriault Aeby Groux Genes specifically modulated sensitized skins detection model. assay.Toxicol 29: 787-802Crossref (80) Harding 2021Harding Murdoch Danby Hasan M.Z. Nakanishi Furuno al.Determination signature tissue-engineered equivalents.JID Innov. 1100011Abstract Full Text PDF (3) 2019Hasan Kitamura Kawai Ohira Mori Shoju al.Transcriptional profiling lactic acid treated epidermis reveals pathways stinging itch.Toxicol 57: 164-173Crossref (13) Saito 2017Saito Takenouchi O. Nukada Miyazawa Sakaguchi An termed EpiSensA broad sets lipophilic pre/pro-haptens.Toxicol 40: 11-25Crossref (33) recently, 2023Harding Colley H.E. Vazquez I.B. al.c-Src marker chemical-induced equivalents.Exp Dermatol. 220-225Crossref (1) Scholar analyzed immediate up-stream signaling cascades upon irritants specific kinases could tested rapid formats. Despite evident progress HSEs, constraint lack neural compartment, isolating stimulus rather than providing orchestrated feedback whole (Basso 2019Basso Serhan Tauber Gaudenzio Peripheral neurons: master regulators mucosal response.Eur Immunol. 49: 1984-1997Crossref Cohen 2020Cohen Kaplan Neuronal regulation cutaneous immunity.J 204: 264-270Crossref (27) Trier 2019Trier A.M. Mack M.R. B.S. neuroimmune axis sensation, inflammation, 202: 2829-2835Crossref (36) Scholar).Table 1Commercially Available Full-Thickness HSECompanySystemRegional AvailabilityReferenceEpiSkin, Lyon, FranceT-SkinGlobalBataillon 2019Bataillon Lelièvre Chapuis Thillou Autourde J.B. Durand al.Characterization thickness model, T-SkinTM, investigations anti-aging compounds.Int 2240Crossref Luu-The 2009Luu-The V. Duche Ferraris Meunier J.R. Leclaire Labrie Expression phases 1 metabolizing enzymes Episkin.J Steroid Biochem 2009; 116: (75) ScholarMatTek, Ashland, MAEpiDermFTGlobalMallampati 2010Mallampati Patlolla R.R. Agarwal Babu R.J. Hayden Klausner al.Evaluation thickness-300 (EFT-300) aliphatic hydrocarbons.Toxicol 24: 669-676Crossref ScholarPhenion, Henkel AG KGaA, Düsseldorf, GermanyPhenion FTEurope (and wider1More specifically, supply places reachable courier service within 72 hours.)Pinto 2022Pinto Trink Giuliani Rinaldi Protective sunscreen (50+) octatrienoic 0.1% actinic keratosis UV damages.J Investig Med. 70: 92-98Crossref ScholarSterlab, Vallauris, FranceFull-thickness skin——Abbreviation: HSE, equivalent.1 hours. Open table tab Abbreviation: equivalent. academia, persisting efforts made sophisticate increase experimental throughput complexity, while methodological aspects faithfully diseases. Here, large collaborative networks formed, similar European Network Modeling (NETSKINMODELS) EU COST Action (CA21108, 2022-2026) over 330 participants 40 countries both academia industry united. With this review, members NETSKINMODELS now stage current developments knowledge technology gaps guidelines resources later fuel implementation academic industrial research. earlier-mentioned properly resemble physiopathology presence circulatory flow imitating vessels distributes nutrients other molecules. addition, natural growth occurs simultaneously body exposed multiple stresses conditions. Therefore, diverse dynamic microfluidic devices stimulate facilitate key tissues vitro, example, bioreactors chip (SoC) 2a). projected induce vivo–like biophysiological at bench scale stimulate, mature, monitor, prolong healthy duration. stretch-based bioreactors—either unidirectional, bidirectional, radial force—to mature basement (Tokuyama 2015Tokuyama Nagai Takahashi Kimata Naruse Mechanical stretch increases develops membrane.PLoS One. 10e0141989Crossref (44) stratum corneum (Jung 2016Jung M.H. Jung S.M. H.S. Co-stimulation HaCaT mechanical stress air-exposure device.Sci Rep. 2016; 633889Crossref (23) stiffer dermis (Wahlsten 2021Wahlsten Rütsche Nanni Giampietro Biedermann Reichmann al.Mechanical stimulation induces fibroblast proliferation accelerates early maturation substitutes.Biomaterials. 273120779Crossref wrinkled (Lim 2018Lim Song H.J. Choi K.C. Park al.Development skin-on-a-chip (WSOC) cyclic uniaxial stretching.J Ind Eng Chem. 68: 238-245Crossref (37) Because maintenance process involving biophysiological, chemical, stimuli, tend simplify focus introduction few design development. Nowadays, can find bioreactor techniques cultivation models: perfusion 2b–h). Perfusion fresh media same time removal waste metabolites. enable shear cells, produced endothelium, responsible various protein synthesis division. channel placed just below (Lee 2017Lee Jin Y.K. Sung G.Y. Chung Construction multicellular model.Biomed Microdevices. 19: 22Crossref (97) Rimal 2021Rimal Marquardt Nevolianis Djeljadini Marquez A.B. Huth al.Dynamic enables long-term 3-D models.Appl Mater Today. 25101213Google 2018Song Lim Chun Lee skin-equivalent pump-less chip.J 60: 355-359Crossref (38) Scholar) around (Sriram 2018Sriram Alberti Dancik Feng Z. al.Full-thickness skin-on-chip enhanced morphogenesis function.Mater 326-340Crossref (185) passively gravity-based platform peristaltic pump (Rimal Sriram across dermal compartment vascular network (Mori 2017Mori Morimoto Takeuchi channels chip.Biomaterials. 48-56Crossref Owing variable demands needed desired dedicated HSEs. Nevertheless, ample evidence benefits cultures, soon expect shift cultures. will lead cheaper, For this, upcoming simplification, ease use, less manual input modular integration sensors, apparatus single platform. trends require realistic environment analysis. succeed first, macroscale limited scalability. regard, SoCs miniaturized microflows, forces, gradients obtain accurate treatments drugs (Abaci 2016Abaci Guo Coffman Gillette W.-H. Sia S.K. constructs spatially controlled vasculature iPSC-derived endothelial cells.Adv Healthc 5: 1800-1807Crossref 2018Mori Perfusable stretchable skin-equivalent.Biofabrication. 11011001Crossref (51) Scholar, SoC platforms divided groups, depending inside 2). First, microfluidics biopsies transferred SoCs. original definition organ-on-a-chip given Ingber (Bhatia Ingber, 2014Bhatia D.E. Microfluidic organs-on-chips.Nat 760-772Crossref (2406) shown good when transdermal transport bacterial infections 2015Abaci Gledhill Christiano Shuler M.L. Pumpless equivalents.Lab Chip. 882-888Crossref 2019aKim J.J. Ellett Thomas C.N. Jalali Anderson Irimia microscale, full-thickness, simulating neutrophil responses antibiotic treatments.Lab 3094-3103Crossref commonly multiorgan-on-a-chip (Maschmeyer 2015Maschmeyer Lorenz Schimek Hasenberg Ramme A.P. Hübner four-organ-chip interconnected co-culture intestine, liver, kidney 2688-2699Crossref Wagner 2013Wagner Materne E.M. Brincker Süssbier U. Frädrich Busek multi-organ-chip substance proven liver co-culture.Lab 2013; 13: 3538-3547Crossref second group refers those directly device. monolayers, either (Ramadan Ting, 2016Ramadan Q. Ting F.C. micro-physiological immune-competent skin.Lab 1899-1908Crossref monolayers (Wufuer 2016Wufuer Hur Jeon B.J. T.H. al.Skin-on-a-chip edema drug-based treatment.Sci 637471Crossref (234) groups gone step further, generating structures device, single-differentiated (Zhang 2021Zhang Chen Zhang Wang X. Ouyang Zhu al.Construction high fidelity epidermis-on-a-chip scalable evaluation.Lab 3804-3818Crossref 2Summary Dynamic Models Found LiteratureType PlatformDermal MatrixCellsApplicationReferenceMicrofluidic platformNoneNormal keratinocytesNHKs cultureO'Neill 2008O'Neill A.T. Monteiro-Riviere Walker G.M. Characterization culture.Cytotechnology. 2008; 56: 197-207Crossref ScholarVascularized HSECollagenNormal + HUVECsPercutaneous absorption, permeabilityMori HSECollagenPrimary

Language: Английский

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From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

Current Oncology, Journal Year: 2024, Volume and Issue: 31(2), P. 778 - 800

Published: Feb. 1, 2024

Molecular biology studies of uveal melanoma have resulted in the development novel immunotherapy approaches including tebentafusp—a T cell–redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined is developed as well with bifunctional checkpoint inhibitory cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination IKKb-matured dendritic cells, or autologous cells loaded tumor RNA. Another potential approach to treat UM could be based on receptor engineering rather than antibody modification. Immune-mobilizing monoclonal receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis therapy same molecule bring hope this research.

Language: Английский

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The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 913 - 913

Published: Feb. 23, 2024

Melanoma progression is a multistep evolution from common melanocytic nevus through radial superficial growth phase, the invasive vertical phase finally leading to metastatic dissemination into distant organs. aggressiveness largely depends on propensity metastasize, which means capacity escape physiological microenvironment since tissue damage due primary melanoma lesions generally modest. Physiologically, epidermal melanocytes are attached basement membrane, and their adhesion/migration under control of surrounding keratinocytes. Thus, compartment represents first responsible for spread. This complex process involves cell-cell contact broad range secreted bioactive molecules. Invasion, or at beginning microinvasion, implies breakdown dermo-epidermal membrane followed by migration neoplastic cells in papillary dermis. Correspondingly, several experimental evidences documented structural functional rearrangement entire neoplasm that some way reflects atypia tumor cells. Lastly, must support proliferation survival outside normal epidermal-melanin units. task presumably mostly delegated fibroblasts ultimately self-autonomous review will discuss remodeling occurs epidermis during formation as well skin changes occur independently hyperproliferation having possible pro-tumoral features.

Language: Английский

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Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(5)

Published: May 20, 2024

Backgrounds: Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes the basal layer of epidermis. Dysregulation this process can lead to various skin disorders, such as hyperpigmentation hypopigmentation. Therefore, present study investigated effect ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. Methods: Firstly, yield proximate compositional analysis samples were conducted. The SHUE on cell viability has been evaluated using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, melanin content cellular tyrosinase activity α-MSH-stimulated examined. Western blot was carried out investigate protein expression levels microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), protein-2 (TRP2). In addition, extracellular signal-regulated kinase (ERK) assessed via blotting. Results: As per analysis, contained highest average a dry basis at 28.70 ± 3.21%. findings showed that reduced Additionally, MITF, TRP1, TRP2 significantly downregulated treatment Moreover, upregulated phosphorylation ERK AKT experiments conducted inhibitor (PD98059) revealed depends signaling cascade. Conclusion: These results suggest an anti-melanogenic be used material formulation cosmetics related whitening lightening.

Language: Английский

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The Melanocyte and Nerve Fiber Cross‐Talk, Facilitated Also by Semaphorin‐4A, Enhances UV‐B‐Induced Melanogenesis

Pigment Cell & Melanoma Research, Journal Year: 2025, Volume and Issue: 38(1)

Published: Jan. 1, 2025

ABSTRACT Epidermal melanocytes form synaptic‐like contacts with cutaneous nerve fibers, but the functional outcome of these connections remains elusive. In this pilot study we used our fully humanized re‐innervated skin organ culture model to investigate melanocyte‐nerve fiber interactions in UV‐B‐induced melanogenesis. UV‐B‐irradiation significantly enhanced melanin content and tyrosinase activity compared non‐innervated controls, indicating that neuronal presence is essential for exacerbating pigmentation upon UV‐B irradiation long‐term culture. Comparative transcriptomic analysis between laser‐capture‐microdissected from freshly embedded human published microarray data on vitro primary identified Semaphorin‐4A (SEMA4A) as possible mediator fibers interactions. SEMA4A protein levels Gp100 + ‐epidermal were higher skin, reduced by treatment. Analysis showed expression 24 h after while secretion into medium was increased. Beta‐tubulin axon growth sensory neurons stimulated conditioned media (CM) irradiated melanocytes. When neuronal‐conditioned transferred fresh melanocytes, increased, only if had been treated CM These findings highlight importance melanocyte‐neuron melanogenesis suggest secreted proteins (e.g., SEMA4A) can function a novel target treat hypo‐ hyperpigmentation disorders.

Language: Английский

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