A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

Kumar, Vinod; Bouameur, Jamal-Eddine; Bär, Janina; Rice, Robert H.; Hornig-Do, Hue-Tran; Roop, Dennis R.; Schwarz, Nicole; Brodesser, Susanne; Thiering, Sören; Leube, Rudolf E.; Wiesner, Rudolf J.; Vijayaraj, Preethi; Brazel, Christina B.; Heller, Sandra; Binder, Hans; Löffler-Wirth, Henry; Seibel, Peter; Magin, Thomas M.

doi:10.1083/jcb.201404147

Cited by 83 publications

(95 citation statements)

References 125 publications

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“…[15] Sample data were analyzed using X!Tandem (Cyclone 2013.02.01.1) to search a Uniprot human database appended to a database of common non-human contaminants (cRAP, common Repository of Adventitious Proteins database, http://www.thegpm.org/crap/). Both were appended to an identical but reversed database for estimating false discovery rates (137,120 entries total), assuming the digestion enzyme was trypsin.…”

Section: Methodsmentioning

confidence: 99%

Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII

Phillips

Cánovas

et al. 2016

Environ. Chem.

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SbIII and AsIII are known to exhibit similar chemical properties, but the degree of similarity in their effects on biological systems merits further exploration. Present work compares the responses of human epidermal keratinocytes, a known target cell type for arsenite-induced carcinogenicity, to these metalloids after treatment for a week at environmentally relevant concentrations. Previous work with these cells has shown that arsenite and antimonite have parallel effects in suppressing differentiation, altering levels of several critical enzymes and maintaining colony forming ability. More globally, protein profiling now reveals parallels in SbIII and AsIII effects. The more sensitive technique of transcriptional profiling also shows considerable parallels. Thus, gene expression changes were almost entirely in the same directions for the two treatments, although the degree of change was sometimes significantly different. Inspection of the changes revealed that RYR1 and LRIG1 were among the genes strongly suppressed, consistent with reduced calcium-dependent differentiation and maintenance of EGF-dependent proliferative potential. Moreover, levels of miRNAs in the cells were altered in parallel, with nearly 90% of the 198 most highly expressed ones being suppressed. Among these was miR-203, which is known to decrease proliferative potential. Finally, both SbIII and AsIII were seen to attenuate bone morphogenetic protein 6 induction of dual specificity phosphatases 2 and 14, consistent with maintaining epidermal growth factor receptor signaling. These findings raise the question whether SbIII, like AsIII, could act as a human skin carcinogen.

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Section: Methodsmentioning

confidence: 99%

Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII

Phillips

Cánovas

et al. 2016

Environ. Chem.

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“…To overcome the latter, mice lacking the entire KtyI and KtyII genes in their epidermis were generated, in addition to mice lacking both KRT1 and KRT10. Such mice developed a fully stratified epidermis but died perinatally because of extensive epidermal damage (Wallace et al 2012;Bar et al 2014;Kumar et al 2015). Most importantly, these mice showed diminished intercellular adhesion and significantly smaller desmosomes.…”

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

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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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“…Once the cells reach a state of terminal differentiation, they will only keep structural elements as mechanical barrier[3]. At present, an increasing number of studies conducted on in vitro skin models and in transgenic mice revealed a close relationship between epidermis and keratin[4–6]. …”

Section: Introductionmentioning

confidence: 99%

Role of keratin 24 in human epidermal keratinocytes

et al. 2017

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Keratin 24 (K24) is a new kind of keratin genes, which encodes a novel keratin protein, K24 that bears high similarity to the type I keratins and displays a unique expression profile. However, the role of K24 is incompletely understood. In our study, we investigated the localization of K24 within the epidermis and possible functions. Keratin 24 was found to be modestly overexpressed in senescent keratinocytes and was mainly restricted to the upper stratum spinosum of epidermis. The protein was required for terminal differentiation upon CaCl2-induced differentiation. In vitro results showed that increased K24 in keratinocytes dramatically changed the differentiation of primary keratinocytes. It also inhibited cell survival by G1/S phase cell cycle arrest and induced senescence, autophagy and apoptosis of keratinocytes. In addition, K24 activated PKCδ signal pathway involving in cellular survival. In summary, K24 may be suggested as a potential differentiation marker and anti-proliferative factor in the epidermis.

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A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

Abstract: Epidermal keratin filaments are important components and organizers of the cornified envelope and regulate mitochondrial metabolism by modulating their membrane composition.

Cited by 83 publications

References 125 publications

Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII

Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Role of keratin 24 in human epidermal keratinocytes

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