Wnt/β-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes

Kosumi, Hideyuki; Watanabe, Mika; Shinkuma, Satoru; Nohara, Takuma; Fujimura, Yoshihiko; Tsukiyama, Tadasuke; Donati, Giacomo; Iwata, Hiroaki; Nakamura, Hideki; Ujiie, Hideyuki; Natsuga, Ken

doi:10.1016/j.jid.2021.10.018

Cited by 12 publications

(5 citation statements)

References 50 publications

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“…After exploring the difference in the communication pathways between groups, we also analyzed the interaction between immune cells and stromal cells to for better understanding the poor performance of ECM scaffolds in wound healing. In aged group, although Mchem and Fib_col expressed active PTN 67 and FGF 68 pathways related to epithelial migration and proliferation towards IFE_B, Mbm around the scaffold showed lower strength of WNT 69,70 and GDF 71 pathways, which seems to dominate the IFE_B proliferation and migration activities, associated with delayed re-epithelialization. Conversely, Mbm in Young_ECM exhibited more activity through the TWEAK pathway with IFE_B (Fig 5. j), previously known to promote more chemokine secretion by epithelial cells, contributing to the establishment of regenerative microenvironment in turn 72 .…”

Section: Resultsmentioning

confidence: 91%

“…pathways related to epithelial migration and proliferation towards IFE_B, Mbm around the scaffold showed lower strength of WNT69,70 and GDF71 pathways, which seems to dominate the IFE_B proliferation and migration activities, associated with delayed re-epithelialization. Conversely, Mbm in Young_ECM exhibited more activity through the TWEAK pathway with IFE_B (Fig 5. j), previously known to promote more chemokine secretion by epithelial cells, contributing to the establishment of regenerative microenvironment in turn72 .…”

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confidence: 93%

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Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals

Chen,

Chu,

Wang

et al. 2023

Preprint

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Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively elucidate the mechanisms underlying this age-related disparity, we conducted an integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, to explore the complex cellular niches surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we identified and characterized the senescent SPP1+ macrophages may impede the activation of the type L immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.

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Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 93%

Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals

Chen,

Chu,

Wang

et al. 2023

Preprint

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“…Alpha actinin-1 (ACTN1) is an F-actin crosslinking protein, which connects F-actin fibers to focal adhesions and hemidesmosomes through interaction with integrins and Col XVII and thereby promotes matrix adhesion ( Carter et al, 1990 ; Hamill et al, 2015 ). Both BCAM (laminin α5 receptor) and LYPD3 (Ly6/PLAUR domain-containing protein 3) bind laminin in the BM, whereas beta-catenin (CTNNB1) indirectly regulates cell–matrix adhesions by controlling the hemidesmosome assembly through WNT signaling ( Kosumi et al, 2022 ). In addition, the expression of known cell–cell adhesion and ECM organization genes was even further downregulated upon AD skin exposure to Der p 2 pep compared to Der p 2 rec ( Supplementary Figures S3A,B ).…”

Section: Resultsmentioning

confidence: 99%

Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients

Pfisterer,

Wielscher,

Samardzic

et al. 2023

Front. Cell Dev. Biol.

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 cytokine-driven skin inflammation and epithelial barrier dysfunction. The latter is believed to allow the increased penetration of chemicals, toxins, and allergens into the skin. House dust mite allergens, particularly Der p 2, are important triggers in sensitized individuals with AD; the precise actions of these allergens in epithelial biology remain, however, incompletely understood. In this study, we compared the effects of the protein allergen Der p 2 and a mix of non-IgE-reactive Der p 2 peptides on skin cells using patch tests in AD patients and healthy participants. We then analyzed mRNA expression profiles of keratinocytes by single-cell RNA-sequencing. We report that existing barrier deficiencies in the non-lesional skin of AD patients allow deep penetration of Der p 2 and its peptides, leading to local microinflammation. Der p 2 protein specifically upregulated genes involved in the innate immune system, stress, and danger signals in suprabasal KC. Der p 2 peptides further downregulated skin barrier genes, in particular the expression of genes involved in cell–matrix and cell–cell adhesion. Peptides also induced genes involved in hyperproliferation and caused disturbances in keratinocyte differentiation. Furthermore, inflammasome-relevant genes and IL18 were overexpressed, while KRT1 was downregulated. Our data suggest that Der p 2 peptides contribute to AD initiation and exacerbation by augmenting hallmark features of AD, such as skin inflammation, barrier disruption, and hyperplasia of keratinocytes.

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“…Intriguingly, the effect of PKC signaling on COL17 is controversial. In contrast to the above modification mechanism, non-HD COL17 phosphorylation and endocytosis are induced by PKC [51], and HD COL17 destabilization is driven by aPKC [52], which is attributed to the different upstream signaling pathways of PKC activation.…”

Section: Col17 In Escsmentioning

confidence: 92%

“…In terms of the upstream regulatory mechanism of COL17, BP-IgG in BP induces the internalization of COL17 to inhibit its function and reduce cell motility [80], and the aging-induced decline of EGFR inhibits the proteolysis of COL17 to regulate cell motility [48]. It has been confirmed that Wnt signaling affects COL17, which is related to wound repair [52].…”

Section: Col17 In Stem Cell Migrationmentioning

confidence: 95%

Targeting the stem cell niche: role of collagen XVII in skin aging and wound repair

Liu¹,

Ho²,

Wen³

et al. 2022

Theranostics

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The skin epidermis and appendages undergo ongoing renewal throughout life. Stem cells residing in the epidermis and hair follicles are pivotal for sustaining skin homeostasis. The self-renewal ability of stem cells significantly decreases during skin aging but actively increases during wound repair. Residential stem cells reside in niches that provide spatially distinct microenvironments for stem cell maintenance and function. Cell-extracellular matrix (ECM) adhesion is essential for the establishment of niche architecture. Collagen XVII (COL17), as a transmembrane protein constituting hemidesmosomes (HDs), mediates the interactions of stem cells with surrounding cells and the matrix to regulate skin homeostasis, aging and wound repair. This review focuses on the pivotal role of the niche component COL17 in stem cell maintenance and its function in regulation of skin aging and wound repair.

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Wnt/β-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes

Cited by 12 publications

References 50 publications

Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals

Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals

Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients

Targeting the stem cell niche: role of collagen XVII in skin aging and wound repair

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