Epidermal keratin 5 expression and distribution is under dermal influence

Cario‐André, Muriel; Pain, Catherine; Kaulanjan-Checkmodine, P.; Masia, D.R.; Goletti, Delia; Casoli, Vincent; Costet, Pierre; Goussot, J. F.; Guyonnet‐Duperat, Véronique; Bibeyran, Alice; Ezzedine, Khaled; Reymermier, Corinne; André-Frei, V.; Taı̈eb, Alain

doi:10.1111/pcmr.12844

Cited by 7 publications

(8 citation statements)

References 53 publications

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“…Furthermore, there are several recent studies using nude mice for pigmentation research. 71 , 72 , 73 Hence, we selected a normal nude mouse model.…”

Section: Discussionmentioning

confidence: 99%

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

et al. 2021

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Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/β-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the β-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

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“…Furthermore, there are several recent studies using nude mice for pigmentation research. 71 , 72 , 73 Hence, we selected a normal nude mouse model.…”

Section: Discussionmentioning

confidence: 99%

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

et al. 2021

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“…A recent investigation using xenograft mice models elucidated that hyperpigmented xenografts showed K5/FGF2 enhancement and increased K5 expression in all the spinous layers (which was additionally described for DDD patients), whereas K5 was downregulated in hypopigmented xenografts. Moreover, K5 hyperexpression in KCs enhanced melanosome transfer and interactions with cocultivated melanocytes [184].…”

Section: Abnormal Cellular Structures and Functionmentioning

confidence: 98%

Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex

Евтушенко

Beilin

Kosykh

et al. 2021

IJMS

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Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes. Keratin aggregates display impaired dynamics of assembly and diminished solubility and appear to be the trigger for endoplasmic reticulum (ER) stress upon being phosphorylated by MAPKs. Global changes in cellular signaling mainly occur in cases of severe dominant EBS mutations. The spectrum of changes initiated by phosphorylation includes the inhibition of proteasome degradation, TNF-α signaling activation, deregulated proliferation, abnormal cell migration, and impaired adherence of keratinocytes. ER stress also leads to the release of proinflammatory danger-associated molecular pattern (DAMP) molecules, which enhance avalanche-like inflammation. Many instances of positive feedback in the course of cellular stress and the development of sterile inflammation led to systemic chronic inflammation in EBS. This highlights the role of keratin in the maintenance of epidermal and immune homeostasis.

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“…They protect epithelial cells from mechanical damage that may result in cell death and also play a crucial role in processes such as transcriptional regulation, cell adhesion, migration, proliferation, angiogenesis, and inflammation [ 53 ]. In addition, keratin’s role in skin pigmentation has also become of great interest, as recent studies have demonstrated that this intermediate filament protein may be involved in pigmentary disorders [ 54 , 55 ]. The skin is the location of many diverse processes that are essential in maintaining the normal role of key components for the protection and maintenance of homeostasis in the body.…”

Section: Skin Structure and Functionmentioning

confidence: 99%

Phosphatidylglycerol to Treat Chronic Skin Wounds in Diabetes

et al. 2023

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This review proposes the use of dioleoylphosphatidylglycerol (DOPG) to enhance diabetic wound healing. Initially, the characteristics of diabetic wounds are examined, focusing on the epidermis. Hyperglycemia accompanying diabetes results in enhanced inflammation and oxidative stress in part through the generation of advanced glycation end-products (AGEs), in which glucose is conjugated to macromolecules. These AGEs activate inflammatory pathways; oxidative stress results from increased reactive oxygen species generation by mitochondria rendered dysfunctional by hyperglycemia. These factors work together to reduce the ability of keratinocytes to restore epidermal integrity, contributing to chronic diabetic wounds. DOPG has a pro-proliferative action on keratinocytes (through an unclear mechanism) and exerts an anti-inflammatory effect on keratinocytes and the innate immune system by inhibiting the activation of Toll-like receptors. DOPG has also been found to enhance macrophage mitochondrial function. Since these DOPG effects would be expected to counteract the increased oxidative stress (attributable in part to mitochondrial dysfunction), decreased keratinocyte proliferation, and enhanced inflammation that characterize chronic diabetic wounds, DOPG may be useful in stimulating wound healing. To date, efficacious therapies to promote the healing of chronic diabetic wounds are largely lacking; thus, DOPG may be added to the armamentarium of drugs to enhance diabetic wound healing.

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Epidermal keratin 5 expression and distribution is under dermal influence

Cited by 7 publications

References 53 publications

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling

Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex

Phosphatidylglycerol to Treat Chronic Skin Wounds in Diabetes

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