The regional distribution of melanosomes in the epidermis affords a localized intensive photoprotection for basal keratinocyte stem cells

Jiang, Shan; Liao, Zhi-Kai; Jia, Haiyan; Liu, Xiaoming; Wan, Jianxin; Lei, Tiechi

doi:10.1016/j.jdermsci.2021.06.010

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…Melanocytes produce melanin that is packaged in specific organelles (termed melanosomes), endowing the recipient cells with photoprotection 69 . After LP‐12 administration, melanocytes expanded fast in dark phase III and IV (Figure 6A), suggesting that 5‐HT7R was activated in the pigmentation procedure through promoting melanosome maturation and development.…”

Section: Discussionmentioning

confidence: 99%

Serotonin/5‐HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP‐PKA‐MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways

et al. 2023

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Serotonin (5‐HT), a neurotransmitter, is essential for normal and pathological pigmentation processing, and its receptors may be therapeutical targets. The effect and behavior of the 5‐HT7 receptor (5‐HT7R) in melanogenesis in high vertebrates remain unknown. Herein, we examine the role and molecular mechanism of 5‐HT7R in the pigmentation of human skin cells, human tissue, mice, and zebrafish models. Firstly, 5‐HT7R protein expression decreased significantly in stress‐induced depigmentation skin and vitiligo epidermis. Stressed mice received transdermal serotonin 5‐HT7R selective agonists (LP‐12, 0.01%) for 12 or 60 days. Mice might recover from persistent stress‐induced depigmentation. The downregulation of tyrosinase (Tyr), microphthalmia‐associated transcription factor (Mitf) expression, and 5‐HT7R was consistently restored in stressed skin. High‐throughput RNA sequencing showed that structural organization (dendrite growth and migration) and associated pathways were activated in the dorsal skin of LP‐12‐treated animals. 5‐HT7R selective agonist, LP‐12, had been demonstrated to enhance melanin production, dendrite growth, and chemotactic motility in B16F10 cells, normal human melanocytes (NHMCs), and zebrafish. Mechanistically, the melanogenic, dendritic, and migratory functions of 5‐HT7R were dependent on the downstream signaling of cAMP‐PKA‐ERK1/2, JNK MAPK, RhoA/Rab27a, and PI3K/AKT pathway activation. Importantly, pharmacological inhibition and genetic siRNA of 5‐HT7R by antagonist SB269970 partially/completely abolished these functional properties and the related activated pathways in both NHMCs and B16F10 cells. Consistently, htr7a/7b genetic knockdown in zebrafish could blockade melanogenic effects and abrogate 5‐HT‐induced melanin accumulation. Collectively, we have first identified that 5‐HT7R regulates melanogenesis, which may be a targeted therapy for pigmentation disorders, especially those worsened by stress.

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Section: Discussionmentioning

confidence: 99%

Serotonin/5‐HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP‐PKA‐MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways

et al. 2023

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“…To further probe how early senescence-associated pathways are switched on in our hSOC model, we quantified the expression of p21, a well-known inducer of cellular senescence that inhibits the activity of cyclin-dependent kinases. 49,50 qRT-PCR showed a strongly upregulated expression of the cyclin-dependent kinase 1A (CDKN1A) gene, which encodes the p21 protein, 51 already after 24 hours of hSOC (Figure S2). Sirt-1 transcription was also moderately reduced (Figure S2C).…”

Section: Transcriptional Ageing Biomarkersmentioning

confidence: 99%

‘Speed‐ageing’ of human skin in serum‐free organ culture ex vivo: An instructive novel assay for preclinical human skin ageing research demonstrates senolytic effects of caffeine and 2,5‐dimethylpyrazine

van Lessen,

Mardaryev,

Broadley

et al. 2023

Experimental Dermatology

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Preclinical human skin ageing research has been limited by the paucity of instructive and clinically relevant models. In this pilot study, we report that healthy human skin of different age groups undergoes extremely accelerated ageing within only 3 days, if organ‐cultured in a defined serum‐free medium. Quantitative (immuno‐)histomorphometry documented this unexpected ex vivo phenotype on the basis of ageing‐associated biomarkers: the epidermis showed significantly reduced rete ridges and keratinocyte proliferation, sirtuin‐1, MTCO1 and collagen 17a1 protein levels; this contrasted with significantly increased expression of the DNA‐damage marker, γH2A.X. In the dermis, collagen 1 and 3 and hyaluronic acid content were significantly reduced compared to Day 0 skin. qRT‐PCR of whole skin RNA extracts also showed up‐regulated mRNA levels of several (inflamm‐) ageing biomarkers (MMP‐1, ‐2, ‐3, ‐9; IL6, IL8, CXCL10 and CDKN1). Caffeine, a methylxanthine with recognized anti‐ageing properties, counteracted the dermal collagen 1 and 3 reduction, the epidermal accumulation of γH2A.X, and the up‐regulation of CXCL10, IL6, IL8, MMP2 and CDKN1. Finally, we present novel anti‐ageing effects of topical 2,5‐dimethylpyrazine, a natural pheromone TRPM5 ion channel activator. Thus, this instructive, clinically relevant “speed‐ageing” assay provides a simple, but powerful new research tool for dissecting skin ageing and rejuvenation, and is well‐suited to identify novel anti‐ageing actives directly in the human target organ.

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“…This method, described for the first time by Mohanty et al [70], allows the obtention of material for transplantation with the use of the extracting follicles units (FUE) procedure. The suspension obtained in this way includes not only pigment cells but also melanocyte stem cells, keratinocyte stem cells, and hair follicle stem cells [71][72][73]. For this purpose, the authors collected hair in the anagen phase from the occipital area of the scalp, taking care not to damage the hair follicles, which were then rinsed three times with saline with the addition of antibiotics and antifungal agents.…”

Section: Noncultured Follicular Root Sheath Suspensionmentioning

confidence: 99%

Surgical Treatment of Vitiligo

Frączek

Kasprowicz-Furmańczyk

Placek

et al. 2022

IJERPH

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Vitiligo is described as a dermatological condition characterized by pigmentation disorders in both the skin and mucous membranes. Clinically, this disease is characterized by the presence of well-defined white areas of various shapes and sizes, which are a manifestation of a reduced number of melanocytes. Due to the fact that vitiligo can be a significant cosmetic problem for patients, a number of methods are currently available to help fight for a better skin appearance. If all the available non-invasive procedures turn out to be ineffective, surgery can help, which is a very good alternative in the case of difficult-to-treat but stable changes. Both the development of new techniques and modifications to the already available treatment of cell and tissue transplantation give hope to numerous patients around the world. The effectiveness of a particular method is determined by its appropriate selection depending on the lesions undergoing therapy. Each form of surgical intervention has its advantages and disadvantages, which, along with the location or size of the treated hypopigmentation area, should be analyzed by a doctor and discussed with their patient. This article is an overview of the currently available methods of surgical treatment of vitiligo and a comparison of their pros and cons.

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The regional distribution of melanosomes in the epidermis affords a localized intensive photoprotection for basal keratinocyte stem cells

Cited by 5 publications

References 39 publications

Serotonin/5‐HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP‐PKA‐MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways

Serotonin/5‐HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP‐PKA‐MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways

‘Speed‐ageing’ of human skin in serum‐free organ culture ex vivo: An instructive novel assay for preclinical human skin ageing research demonstrates senolytic effects of caffeine and 2,5‐dimethylpyrazine

Surgical Treatment of Vitiligo

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