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

2019 ◽  
Keyword(s):  
Barrier Function ◽  
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 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 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.

A Novel Multi-Action Emollient Plus Cream Improves Skin Barrier Function in Patients with Atopic Dermatitis: In vitro and Clinical Evidence

2021 ◽  
Vol 34 (1) ◽  
pp. 8-18
Author(s):  
Marika Quadri ◽  
Roberta Lotti ◽  
Laura Bonzano ◽  
Silvana Ciardo ◽  
Mario Bruno Guanti ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Randomized Study ◽  
Skin Barrier ◽  
Lower Limbs ◽  
Skin Barrier Function ◽  
Tape Stripping ◽  
Epidermal Thickness ◽  
Epidermal Homeostasis

Background: Emollients capable of restoring the skin barrier function would extend their role beyond basic maintenance therapy in atopic dermatitis (AD). Objectives: Investigate the effect of a novel emollient plus cream (EC; Dermoflan®) on the skin barrier in vitro and in patients with mild-to-moderate AD. Methods: The effect of EC on the skin barrier recovery was evaluated using a tape-stripping (TS) model. After TS, organ cultures were treated with EC (undiluted or diluted 1:1 with water) and analyzed at 18–120 h using hematoxylin and eosin, Oil Red O, immunohistochemical, and immunofluorescent techniques. In a double-blind, randomized study, EC or placebo was applied once daily for 2 months to antecubital folds of the upper and lower limbs of patients with mild-to-moderate AD in clinical remission. Epidermal thickness, vascularization, and epidermal hydration were assessed by optical coherence tomography and corneometry, respectively, at baseline, and 1 and 2 months following treatment initiation. Results: Following TS, EC treatment significantly increased epidermal thickness and lipid content versus diluent in the skin organ culture, as well as claudin-1, involucrin, and caspase-14 expression, suggesting skin barrier repair. EC treatment also decreased keratin-16 expression and increased levels of Toll-like receptors 1 and 2 versus diluent, suggesting involvement in regulating the epidermal immune response. In 20 patients randomized 1:1 to EC or placebo, EC treatment at the elbow fold/popliteal fossa significantly decreased epidermal thickness after 2 months, and the number of blood vessels at the elbow fold after 1 and 2 months, versus placebo. EC significantly improved the skin hydration after 2 months versus baseline. Conclusions: This novel multi-action EC may help to restore epidermal homeostasis and improve the skin of patients with AD. Results indicate that this novel multi-action EC could be a valid adjuvant therapy in patients with AD. Key Message: Novel multi-action emollient cream helps to restore epidermal homeostasis and improves the skin affected by AD.

Freeze-etch observations on the tight junctions of sertoli cells grown in organ culture with FSH

1978 ◽  
Vol 36 (2) ◽  
pp. 340-341
Author(s):  
Rita Meyer ◽  
Zoltan Posalaky ◽  
Dennis Mcginley
Keyword(s):  
Organ Culture ◽  
Tight Junctions ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Barrier Function ◽  
Cell Junction ◽  
Intramembranous Particles ◽  
Junctional Complexes ◽  
Oriented Parallel

The Sertoli cell tight junctional complexes have been shown to be the most important structural counterpart of the physiological blood-testis barrier. In freeze etch replicas they consist of extensive rows of intramembranous particles which are not only oriented parallel to one another, but to the myoid layer as well. Thus the occluding complex has both an internal and an overall orientation. However, this overall orientation to the myoid layer does not seem to be necessary to its barrier function. The 20 day old rat has extensive parallel tight junctions which are not oriented with respect to the myoid layer, and yet they are inpenetrable by lanthanum. The mechanism(s) for the control of Sertoli cell junction development and orientation has not been established, although such factors as the presence or absence of germ cells, and/or hormones, especially FSH have been implicated.

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