Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin

Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.

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Effect of Topically Applied Wikstroemia dolichantha Diels on the Development of Atopic Dermatitis-Like Skin Symptoms in Mice

Nutrients ◽

10.3390/nu11040914 ◽

2019 ◽

Vol 11 (4) ◽

pp. 914 ◽

Cited By ~ 1

Author(s):

Jonghwan Jegal ◽

No-June Park ◽

Tae-Young Kim ◽

Sangho Choi ◽

Sang Woo Lee ◽

...

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Immunoglobulin E ◽

Skin Barrier ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Skin Hydration ◽

Interleukin 4 ◽

Skin Barrier Function ◽

Skin Symptoms

Plants of the genus Wikstroemia are traditionally used to treat inflammatory diseases like bronchitis and rheumatoid arthritis. In the present study, the anti-atopic effects of an EtOH extract of Wikstroemia dolichantha (WDE) on oxazolone- and DNCB (2,4-dinitrochlorobenzene)-induced dermatitis in mice were investigated. Both ears of BALB/c mice were exposed to oxazolone, and dorsal skins of SKH-1 hairless mice were sensitized with DNCB to induce acute eczematous atopic skin lesions. 1% WDE was applied daily to oxazolone- and DNCB-induced AD mice for two or three weeks, respectively. Total IL-4 and IgE concentrations in serum, transepidermal water loss (TEWL) and skin hydration were assessed. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to determine the composition of WDE. Dermal application of 1% WDE grossly and histopathologically improved oxazolone- and DNCB-induced AD skin symptoms. Epidermal thickness and mast cell infiltration were significantly lower in animals treated with WDE than in vehicle controls. Furthermore, in addition to reducing DNCB-induced increases in serum IL-4 (interleukin 4) and IgE (immunoglobulin E) levels, WDE also decreased TEWL and increased skin hydration (indicative of improved skin barrier function). The four flavonoids taxifolin, aromadendrin, padmatin and chamaejasmine were tentatively identified in WDE by HPLC-DAD/QTOF-MS. The above results show WDE protected against oxazolone- and DNCB-induced AD in mice by down-regulating the TH2-associated cytokine IL-4 and improving skin barrier function and suggest WDE might be useful for the management of atopic dermatitis.

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Suppression of DNCB-Induced Atopic Skin Lesions in Mice by Wikstroemia indica Extract

Nutrients ◽

10.3390/nu12010173 ◽

2020 ◽

Vol 12 (1) ◽

pp. 173 ◽

Cited By ~ 3

Author(s):

So-Yeon Lee ◽

No-June Park ◽

Jonghwan Jegal ◽

Beom-Geun Jo ◽

Sangho Choi ◽

...

Keyword(s):

Atopic Dermatitis ◽

Chinese Medicine ◽

Inflammatory Diseases ◽

Ethanolic Extract ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Hairless Mice ◽

Cutaneous Inflammation ◽

Atopic Skin ◽

Dermal Administration

Wikstroemia indica (L.) C.A. Mey. is used in traditional Chinese medicine to treat inflammatory diseases such as arthritis and bronchitis. In this study, we aimed to investigate the effects of an ethanolic extract of W. indica on cutaneous inflammation in mice with 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). Dermal administration of W. indica ethanolic extract to DNCB-sensitized hairless mice with dermatitis, for two weeks, reduced erythema, scaling, and edema. Skin hydration was improved and transepidermal water loss was reduced at a W. indica concentration of 1%. Furthermore, W. indica also significantly reduced serum IgE and IL-4 concentrations in our mouse model. These results suggest that W. indica has potential as a topical treatment for AD and as an adjunctive agent to control AD.

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EGFR regulation of epidermal barrier function

Physiological Genomics ◽

10.1152/physiolgenomics.00176.2011 ◽

2012 ◽

Vol 44 (8) ◽

pp. 455-469 ◽

Cited By ~ 29

Author(s):

Quynh T. Tran ◽

Lawrence H. Kennedy ◽

Sandra Leon Carrion ◽

Sridevi Bodreddigari ◽

Shirlean B. Goodwin ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Barrier Function ◽

Skin Diseases ◽

Transepidermal Water Loss ◽

Epidermal Differentiation ◽

Keratinocyte Differentiation ◽

Disease Genes ◽

Epidermal Barrier ◽

Epidermal Growth

Keratinocyte terminal differentiation is the process that ultimately forms the epidermal barrier that is essential for mammalian survival. This process is controlled, in part, by signal transduction and gene expression mechanisms, and the epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Using microarray analysis of a confluent cell density-induced model of keratinocyte differentiation, we identified 2,676 genes that are regulated by epidermal growth factor (EGF), a ligand of the EGFR. We further discovered, and separately confirmed by functional assays, that EGFR activation abrogates all of the known essential processes of keratinocyte differentiation by 1) decreasing the expression of lipid matrix biosynthetic enzymes, 2) regulating numerous genes forming the cornified envelope, and 3) suppressing the expression of tight junction proteins. In organotypic cultures of skin, EGF acted to impair epidermal barrier integrity, as shown by increased transepidermal water loss. As defective epidermal differentiation and disruption of barrier function are primary features of many human skin diseases, we used bioinformatic analyses to identify genes that are known to be associated with skin diseases. Compared with non-EGF-regulated genes, EGF-regulated genes were significantly enriched for skin disease genes. These results provide a systems-level understanding of the actions of EGFR signaling to inhibit keratinocyte differentiation, providing new insight into the role of EGFR imbalance in skin pathogenesis.

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Faculty Opinions recommendation of Skin barrier function in healthy subjects and patients with atopic dermatitis in relation to filaggrin loss-of-function mutations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.6532956.6663054 ◽

2010 ◽

Author(s):

Eric Simpson

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Healthy Subjects ◽

Skin Barrier ◽

Skin Barrier Function ◽

Loss Of Function

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The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

Current Medicinal Chemistry ◽

10.2174/0929867324666171106164916 ◽

2019 ◽

Vol 25 (40) ◽

pp. 5503-5511 ◽

Cited By ~ 5

Author(s):

Abdulaziz Alhasaniah ◽

Michael J. Sherratt ◽

Catherine A. O'Neill

Keyword(s):

Ultraviolet Radiation ◽

Barrier Function ◽

Molecular Mechanisms ◽

Transepidermal Water Loss ◽

Protective Effects ◽

Barrier Dysfunction ◽

Epidermal Barrier ◽

Positive Effects ◽

Terrestrial Mammals ◽

The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

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Neonatal Birthmarks at the 4 Central Hospitals in Vientiane Capital, Lao PDR

Global Pediatric Health ◽

10.1177/2333794x21990908 ◽

2021 ◽

Vol 8 ◽

pp. 2333794X2199090

Author(s):

Vilounna Sanaphay ◽

Sourideth Sengchanh ◽

Alongkone Phengsavanh ◽

Anousavanh Sanaphay ◽

Leelawadee Techasatian

Keyword(s):

Sebaceous Gland ◽

Neonatal Period ◽

Lao Pdr ◽

Skin Lesions ◽

Medical Advice ◽

Point Of View ◽

Parental Anxiety ◽

Skin Disorders ◽

Clinical Point ◽

Therapeutic Procedures

Newborn skin disorders are quite common and happen to occur during the neonatal period. Most of the birthmarks are transient; however, worried parents often seek medical advice from their child’s physician regarding skin lesions. Thus, it is important to differentiate the skin lesions from pathologic ones to avoid unnecessary diagnostic or therapeutic procedures. This is the first published study in Lao neonates that carried out the data from 4 central hospitals in Vientiane Capital, Lao PDR from September 2019 to February 2020. Among 500 neonates, Sebaceous gland hyperplasia (53%), Mongolian patches (46.6%), and Erythema toxicum neonatorum (30%) were the 3 most common cutaneous conditions found in the Lao newborns. From a clinical point of view, these findings are often a source of parental anxiety and medical concern for inexperienced clinicians.

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Stratum Corneum Barrier Function in the Elderly-An Evaluation of Irritant Response to Sodium Lauryl Sulfate by Visual Scoring and Transepidermal Water Loss Measurements. Anastasia B. Cua, Klaus-P. Wilhelm, and Howard I. Maibach, Department of Dermatology, University of California, San Francisco, CA.

Dermatitis ◽

10.1097/01206501-199009000-00020 ◽

1990 ◽

Vol 1 (3) ◽

pp. 202

Author(s):

&NA;

Keyword(s):

Stratum Corneum ◽

San Francisco ◽

Water Loss ◽

Barrier Function ◽

Sodium Lauryl Sulfate ◽

The Elderly ◽

Transepidermal Water Loss ◽

University Of California ◽

Lauryl Sulfate ◽

Visual Scoring

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Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

Journal of Clinical Medicine ◽

10.3390/jcm10020359 ◽

2021 ◽

Vol 10 (2) ◽

pp. 359 ◽

Cited By ~ 1

Author(s):

Trinidad Montero-Vilchez ◽

María-Victoria Segura-Fernández-Nogueras ◽

Isabel Pérez-Rodríguez ◽

Miguel Soler-Gongora ◽

Antonio Martinez-Lopez ◽

...

Keyword(s):

Atopic Dermatitis ◽

Disease Severity ◽

Water Loss ◽

Barrier Function ◽

Skin Barrier ◽

Transepidermal Water Loss ◽

Diagnostic Tools ◽

Psoriatic Skin ◽

Skin Barrier Function ◽

Healthy Controls

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

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