scholarly journals Skin permeability barrier formation by the ichthyosis-causative gene FATP4 through formation of the barrier lipid ω-O-acylceramide

2020 ◽  
Vol 117 (6) ◽  
pp. 2914-2922 ◽  
Author(s):  
Haruka Yamamoto ◽  
Miku Hattori ◽  
Walee Chamulitrat ◽  
Yusuke Ohno ◽  
Akio Kihara
Keyword(s):  
Skin Barrier ◽  
Human Keratinocytes ◽  
Skin Permeability ◽  
Permeability Barrier ◽  
Barrier Dysfunction ◽  
Causative Gene ◽  
Synthetic Pathway ◽  
Barrier Formation ◽  
Chain Lengths

The epidermis-specific lipid acylceramide plays a pivotal role in the formation of the permeability barrier in the skin; abrogation of its synthesis causes the skin disorder ichthyosis. However, the acylceramide synthetic pathway has not yet been fully elucidated: Namely, the acyl-CoA synthetase (ACS) involved in this pathway remains to be identified. Here, we hypothesized it to be encoded by FATP4/ACSVL4, the causative gene of ichthyosis prematurity syndrome (IPS). In vitro experiments revealed that FATP4 exhibits ACS activity toward an ω-hydroxy fatty acid (FA), an intermediate of the acylceramide synthetic pathway. Fatp4 knockout (KO) mice exhibited severe skin barrier dysfunction and morphological abnormalities in the epidermis. The total amount of acylceramide in Fatp4 KO mice was reduced to ∼10% of wild-type mice. Decreased levels and shortening of chain lengths were observed in the saturated, nonacylated ceramides. FA levels were not decreased in the epidermis of Fatp4 KO mice. The expression levels of the FA elongase Elovl1 were reduced in Fatp4 KO epidermis, partly accounting for the reduction and shortening of saturated, nonacylated ceramides. A decrease in acylceramide levels was also observed in human keratinocytes with FATP4 knockdown. From these results, we conclude that skin barrier dysfunction observed in IPS patients and Fatp4 KO mice is caused mainly by reduced acylceramide production. Our findings further elucidate the molecular mechanism governing acylceramide synthesis and IPS pathology.

scholarly journals EFFECT OF MENTHOL ON THE TRANSDERMAL PERMEATION OF ACECLOFENAC FROM MICROEMULSION FORMULATION

2019 ◽  
pp. 117-122
Author(s):  
Abdul Baquee Ahmed ◽  
Gouranga Das
Keyword(s):  
Droplet Size ◽  
Skin Permeation ◽  
Peak Height ◽  
Skin Permeability ◽  
Permeability Barrier ◽  
Microemulsion Formulation ◽  
Transdermal Permeation ◽  
Ir Studies ◽  
Ft Ir

Objective: The aim of this investigation was to enhance the transdermal permeation of aceclofenac (ACF) from microemulsion formulation using menthol as a natural permeation enhancer. Methods: Microemulsion containing 2% w/v of ACF was prepared by a titration method with different concentration of oil, surfactant and co-surfactant. The prepared microemulsion was evaluated for droplet size, viscosity, pH and in vitro skin permeation studies. Menthol at 3-8% w/w was added to the selected microemulsion formulation and their effect on skin permeation was evaluated across rat epidermis using modified Keshary-Chien diffusion cell. The Fourier transform infrared spectroscopy (FT-IR) was performed to understand the regulation action of menthol in the skin permeability barrier. Results: The average droplet size of the microemulsion was found to be 89.4±2.12 to 175.2±3.10 nm. The transdermal flux of the microemulsion containing 8% w/w menthol showed 2.9 fold increases in transdermal flux of ACF compared with the formulation without menthol. Result of FT-IR studies showed decrease in peak height of the symmetric and asymmetric C-H stretching vibrations may be because of the extraction of the stratum corneum (SC) lipids and the alteration of the skin permeability barrier. Conclusion: This result suggests that menthol significantly enhanced the transdermal permeation of ACF and may be an effective natural penetration enhancer for transdermal delivery of the drug.

scholarly journals A Case of IFAP Syndrome with Severe Atopic Dermatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Catarina Araújo ◽  
Miguel Gonçalves-Rocha ◽  
Cristina Resende ◽  
Ana Paula Vieira ◽  
Celeste Brito
Keyword(s):  
Missense Mutation ◽  
Histopathological Examination ◽  
Genetic Disorder ◽  
Phenotypic Expression ◽  
Regulatory System ◽  
Hair Follicles ◽  
Skin Permeability ◽  
Severe Atopic Dermatitis ◽  
Permeability Barrier ◽  
First Year Of Life

Introduction.The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia.Case Report.A three-month-old Caucasian, male patient was observed with noncicatricial universal alopecia and persistent eczema from birth. He had dystrophic nails, spiky follicular hyperkeratosis, and photophobia which became apparent at the first year of life. Short stature and psychomotor developmental delay were also noticed. Histopathological examination of skin biopsy on left thigh showed epidermis with irregular acanthosis, lamellar orthokeratotic hyperkeratosis, and hair follicles fulfilled by parakeratotic hyperkeratosis. The chromosomal study showed a karyotype 46, XY. Total IgE was 374 IU/mL. One missense mutation c.1360G>C (p.Ala454Pro) in hemizygosity was detected on theMBTPS2gene thus confirming the diagnosis of IFAP syndrome.Conclusions.We describe a boy with a typical clinical presentation of IFAP syndrome and severe atopic manifestations. A novel missense mutation c.1360G>C (p.Ala454Pro) inMBTPS2gene was observed. The phenotypic expression of disease is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol and endoplasmic reticulum homeostasis. It can cause epithelial disturbance with failure in differentiation of epidermal structures and abnormal skin permeability barrier. However, no correlation phenotype/genotype could be established.

Phosphodiesterase inhibitors block the acceleration of skin permeability barrier repair by red light

2011 ◽  
Vol 20 (7) ◽  
pp. 568-571 ◽  
Author(s):  
Makiko Goto ◽  
Kazuyuki Ikeyama ◽  
Moe Tsutsumi ◽  
Sumiko Denda ◽  
Mitsuhiro Denda
Keyword(s):  
Red Light ◽  
Phosphodiesterase Inhibitors ◽  
Skin Permeability ◽  
Permeability Barrier ◽  
Barrier Repair

scholarly journals Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation

2015 ◽  
Vol 112 (25) ◽  
pp. 7707-7712 ◽  
Author(s):  
Yusuke Ohno ◽  
Shota Nakamichi ◽  
Aya Ohkuni ◽  
Nozomi Kamiyama ◽  
Ayano Naoe ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Lipid Analysis ◽  
Skin Permeability ◽  
Carbon Chain Length ◽  
Permeability Barrier ◽  
Type I ◽  
P450 Gene ◽  
Barrier Formation

A skin permeability barrier is essential for terrestrial animals, and its impairment causes several cutaneous disorders such as ichthyosis and atopic dermatitis. Although acylceramide is an important lipid for the skin permeability barrier, details of its production have yet to be determined, leaving the molecular mechanism of skin permeability barrier formation unclear. Here we identified the cytochrome P450 gene CYP4F22 (cytochrome P450, family 4, subfamily F, polypeptide 22) as the long-sought fatty acid ω-hydroxylase gene required for acylceramide production. CYP4F22 has been identified as one of the autosomal recessive congenital ichthyosis-causative genes. Ichthyosis-mutant proteins exhibited reduced enzyme activity, indicating correlation between activity and pathology. Furthermore, lipid analysis of a patient with ichthyosis showed a drastic decrease in acylceramide production. We determined that CYP4F22 was a type I membrane protein that locates in the endoplasmic reticulum (ER), suggesting that the ω-hydroxylation occurs on the cytoplasmic side of the ER. The preferred substrate of the CYP4F22 was fatty acids with a carbon chain length of 28 or more (≥C28). In conclusion, our findings demonstrate that CYP4F22 is an ultra-long-chain fatty acid ω-hydroxylase responsible for acylceramide production and provide important insights into the molecular mechanisms of skin permeability barrier formation. Furthermore, based on the results obtained here, we proposed a detailed reaction series for acylceramide production.

scholarly journals Topical Application of TRPA1 Agonists and Brief Cold Exposure Accelerate Skin Permeability Barrier Recovery

2010 ◽  
Vol 130 (7) ◽  
pp. 1942-1945 ◽  
Author(s):  
Mitsuhiro Denda ◽  
Moe Tsutsumi ◽  
Makiko Goto ◽  
Kazuyuki Ikeyama ◽  
Sumiko Denda
Keyword(s):  
Topical Application ◽  
Cold Exposure ◽  
Skin Permeability ◽  
Permeability Barrier

scholarly journals The epidermal barrier function is dependent on the serine protease CAP1/Prss8

2005 ◽  
Vol 170 (3) ◽  
pp. 487-496 ◽  
Author(s):  
Céline Leyvraz ◽  
Roch-Philippe Charles ◽  
Isabelle Rubera ◽  
Marjorie Guitard ◽  
Samuel Rotman ◽  
...  
Keyword(s):  
Serine Protease ◽  
Barrier Function ◽  
Serine Proteases ◽  
Proteolytic Enzymes ◽  
Transepidermal Water Loss ◽  
Skin Barrier Function ◽  
Skin Permeability ◽  
Permeability Barrier ◽  
Differentiation Markers ◽  
Skin Development

Serine proteases are proteolytic enzymes that are involved in the regulation of various physiological processes. We generated mice lacking the membrane-anchored channel-activating serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth. They presented a lower body weight and exhibited severe malformation of the stratum corneum (SC). This aberrant skin development was accompanied by an impaired skin barrier function, as evidenced by dehydration and skin permeability assay and transepidermal water loss measurements leading to rapid, fatal dehydration. Analysis of differentiation markers revealed no major alterations in CAP1/Prss8-deficient skin even though the epidermal deficiency of CAP1/Prss8 expression disturbs SC lipid composition, corneocyte morphogenesis, and the processing of profilaggrin. The examination of tight junction proteins revealed an absence of occludin, which did not prevent the diffusion of subcutaneously injected tracer (∼600 D) toward the skin surface. This study shows that CAP1/Prss8 expression in the epidermis is crucial for the epidermal permeability barrier and is, thereby, indispensable for postnatal survival.

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