Keratins K2 and K10 are essential for the epidermal integrity of plantar skin

Keratins are the main intermediate filament proteins of epithelial cells. In keratinocytes of the mammalian epidermis they form a cytoskeleton that resists mechanical stress and thereby are essential for the function of the skin as a barrier against the environment. Here, we performed a comparative genomics study of epidermal keratin genes in terrestrial and fully aquatic mammals to determine adaptations of the epidermal keratin cytoskeleton to different environments. We show that keratins K5 and K14 of the innermost (basal), proliferation-competent layer of the epidermis are conserved in all mammals investigated. In contrast, K1 and K10, which form the main part of the cytoskeleton in the outer (suprabasal) layers of the epidermis of terrestrial mammals, have been lost in whales and dolphins (cetaceans) and in the manatee. Whereas in terrestrial mammalian epidermis K6 and K17 are expressed only upon stress-induced epidermal thickening, high levels of K6 and K17 are consistently present in dolphin skin, indicating constitutive expression and substitution of K1 and K10. K2 and K9, which are expressed in a body site-restricted manner in human and mouse suprabasal epidermis, have been lost not only in cetaceans and manatee but also in some terrestrial mammals. The evolution of alternative splicing of K10 and differentiation-dependent upregulation of K23 have increased the complexity of keratin expression in the epidermis of terrestrial mammals. Taken together, these results reveal evolutionary diversification of the epidermal cytoskeleton in mammals and suggest a complete replacement of the quantitatively predominant epidermal proteins of terrestrial mammals by originally stress-inducible keratins in cetaceans.

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“…2014; Fu et al. 2014; Fischer et al. 2016) and adjacent to sweat glands in human epidermis (Moll et al.…”

Section: Resultsmentioning

confidence: 99%

Differential Evolution of the Epidermal Keratin Cytoskeleton in Terrestrial and Aquatic Mammals

Ehrlich

Fischer

Langbein

et al. 2018

Molecular Biology and Evolution

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“…It was upregulated in several epithelial-derived malignancies, including squamous cell carcinoma ( Gupta et al, 2015 ; Ma et al, 2018 ). KRT2 was found to form a mechanically resilient cytoskeleton and contribute to the skin homeostasis ( Fischer et al, 2016 ). SPRR2F, a cross-linked envelope protein of keratinocytes, providing the protective barrier function ( Cabral et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Signatures of Prognosis Prediction for Melanoma Using a Hypoxia Score

Shou

Yang

et al. 2020

Front. Genet.

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Melanoma is one of the most aggressive cancers. Hypoxic microenvironment affects multiple cellular pathways and contributes to tumor progression. The purpose of the research was to investigate the association between hypoxia and melanoma, and identify the prognostic value of hypoxia-related genes. Based on the GSVA algorithm, gene expression profile collected from The Cancer Genome Atlas (TCGA) was used for calculating the hypoxia score. The Kaplan–Meier plot suggested that a high hypoxia score was correlated with the inferior survival of melanoma patients. Using differential gene expression analysis and WGCNA, a total of 337 overlapping genes associated with hypoxia were determined. Protein-protein interaction network and functional enrichment analysis were conducted, and Lasso Cox regression was performed to establish the prognostic gene signature. Lasso regression showed that seven genes displayed the best features. A novel seven-gene signature (including ABCA12, PTK6, FERMT1, GSDMC, KRT2, CSTA, and SPRR2F) was constructed for prognosis prediction. The ROC curve inferred good performance in both the TCGA cohort and validation cohorts. Therefore, our study determined the prognostic implication of the hypoxia score in melanoma and showed a novel seven-gene signature to predict prognosis, which may provide insights into the prognosis evaluation and clinical decision making.

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“…Cite this article as Cold Spring Harb Perspect Biol 2017;9:a029157 Deletion and/or mutation of other keratin isotypes expressed in different epidermal compartments, either in the mouse or in humans, did not cause cytolysis and skin blistering to the same extent as KRT5 and KRT14, but was typified by altered cell and tissue growth, barrier, and immune defects (Reichelt et al 2001;McGowan et al 2002;Lessard and Coulombe 2012;Roth et al 2012;Fischer et al 2014Fischer et al , 2016Fu et al 2014;Kumar et al 2016;Bouameur and Magin 2017). Transgenic expression of a bundling-competent KRT5/KRT8 chimaera partially rescued KRT5 2/2 mice, whereas expression of bundling-deficient KRT8 did not, providing strong evidence that, in addition to keratin abundancy, isotype-specific properties and keratin network organization are crucial contributors to keratin-mediated stress resilience (Alvarado and Coulombe 2014).…”

Section: Desmosomes and Keratins In Tissue Mechanicsmentioning

confidence: 99%

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Hatzfeld

Keil

Magin

2017

Cold Spring Harb Perspect Biol

114

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Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength.

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Keratins K2 and K10 are essential for the epidermal integrity of plantar skin

Cited by 23 publications

References 37 publications

Differential Evolution of the Epidermal Keratin Cytoskeleton in Terrestrial and Aquatic Mammals

Differential Evolution of the Epidermal Keratin Cytoskeleton in Terrestrial and Aquatic Mammals

Identification of Signatures of Prognosis Prediction for Melanoma Using a Hypoxia Score

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

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