scholarly journals 692 Keratin-14 dependent disulfide bonding contributes to epidermal homeostasis and barrier function through 14-3-3 and Hippo signaling in mouse skin in vivo

2018 ◽  
Vol 138 (5) ◽  
pp. S118
Author(s):  
Y. Guo ◽  
K. Leacock ◽  
V. Ranganathan ◽  
P. Coulombe
Keyword(s):  
Barrier Function ◽  
Mouse Skin ◽  
Hippo Signaling ◽  
Disulfide Bonding ◽  
Keratin 14 ◽  
Epidermal Homeostasis

scholarly journals Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

2019 ◽  
Author(s):  
Yajuan Guo ◽  
Krystynne A. Leacock ◽  
Catherine Redmond ◽  
Vinod Jaskula-Ranga ◽  
Pierre A. Coulombe
Keyword(s):  
Barrier Function ◽  
Type I ◽  
Hippo Signaling ◽  
Disulfide Bonding ◽  
Structural Support ◽  
Skin Keratinocytes ◽  
Keratin 14 ◽  
Barrier Defect ◽  
Epidermal Homeostasis ◽  
And Function

SummaryThe type I intermediate filament (IF) keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at codon 373 (C373A) in Krt14 exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in the epidermis. A proteomics screen identified 14-3-3 as major K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14C373A keratinocytes. Residue C373 in K14, which is conserved in several other type I IFs, is thus revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in the epidermis.

scholarly journals Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yajuan Guo ◽  
Catherine J Redmond ◽  
Krystynne A Leacock ◽  
Margarita V Brovkina ◽  
Suyun Ji ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intermediate Filament Protein ◽  
Hippo Signaling ◽  
Structural Support ◽  
Skin Keratinocytes ◽  
Keratin 14 ◽  
Barrier Defect ◽  
Epidermal Homeostasis ◽  
And Function ◽  
Filament Protein

The intermediate filament protein keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at Krt14’s codon 373 (C373A) exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in epidermis. A proteomics screen identified 14-3-3 as K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14 C373A keratinocytes. Residue C373 in K14, which is conserved in a subset of keratins, is revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in epidermis.

scholarly journals Author response: Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

2020 ◽  
Author(s):  
Yajuan Guo ◽  
Catherine J Redmond ◽  
Krystynne A Leacock ◽  
Margarita V Brovkina ◽  
Suyun Ji ◽  
...  
Keyword(s):  
Barrier Function ◽  
Author Response ◽  
Keratin 14 ◽  
Epidermal Homeostasis

scholarly journals Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Normal Skin ◽  
Skin Lesions ◽  
Hippo Signaling ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Hippo Signaling Pathway ◽  
Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

scholarly journals Activated Kras Alters Epidermal Homeostasis of Mouse Skin, Resulting in Redundant Skin and Defective Hair Cycling

2011 ◽  
Vol 131 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Anandaroop Mukhopadhyay ◽  
Suguna R. Krishnaswami ◽  
Benjamin D.-Y. Yu
Keyword(s):  
Mouse Skin ◽  
Epidermal Homeostasis

scholarly journals Sauna dehydration as a new physiological challenge model for intestinal barrier function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Fernanda Roca Rubio ◽  
Ulrika Eriksson ◽  
Robert J. Brummer ◽  
Julia König
Keyword(s):  
Fatty Acid ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

AbstractThe intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

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