Estimation of peroxisome proliferators – activated receptor γ gene expression in inflammatory skin diseases: atopic dermatitis and psoriasis

Mahgoub, Doaa; Tawdy, Amira El; Metwally, Dina M.; Manar, Amin; Rashed, Laila A.

doi:10.7241/ourd.20142.27

Cited by 4 publications

(5 citation statements)

References 34 publications

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“…Inflammation and an altered epidermal barrier function are characteristics of dermatitis of any origin and researchers Arch Dermatol Res after observing deranged PPAR expression in various dermatitic conditions including atopic dermatitis (AD) suggested their significant role in the pathogenesis of dermatitis [13,17,51]. Chiba et al [13] observed downregulation of PPARa in atopic dermatitis (AD)-like dermatitis in nc/Nga mice.…”

Section: Dermatitismentioning

confidence: 97%

“…Chiba et al [13] observed downregulation of PPARa in atopic dermatitis (AD)-like dermatitis in nc/Nga mice. Atopic dermatitis lesional skin shows nearly 50 % reduction in PPARa expression in comparison to normal skin, and down-regulation of PPARa by influencing the lipid pathway is perhaps involved in development or maintenance of atopic dermatitis [51]. An increased expression of PPARa has been observed in a mouse model of allergic contact dermatitis and PPARa ligands reduce epidermal hyperproliferation and stimulate differentiation.…”

Section: Dermatitismentioning

confidence: 98%

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Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Gupta¹,

Mahajan²,

Mehta³

et al. 2015

Arch Dermatol Res

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Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.

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Section: Dermatitismentioning

confidence: 97%

Section: Dermatitismentioning

confidence: 98%

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Gupta¹,

Mahajan²,

Mehta³

et al. 2015

Arch Dermatol Res

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show abstract

“…The important role of epidermal PPARγ in moderating cutaneous inflammation is seen both by analysis of the differentially expressed genes as well as the observed phenotype. The top GO terms that linked to our data set showed upregulation of multiple inflammatory cytokine and chemokine transcripts, upregulation of genes associated with inflammasome activation (Aim2, Nod2, Nlrp3, Il1f6 and 8, Casp1, Gsdma2, Gsdmc), and the upregulation of keratins associated with inflammatory hyperplasia (e.g., Krt 6,16,17). In addition to the disruption in inflammatory signaling, C57.Pparg-/-epi mice developed spontaneous lesions that are reminiscent of wound healing, atopic dermatitis, and psoriasis.…”

Section: Discussionmentioning

confidence: 97%

“…There is strong evidence that PPARγ may suppress the inflammation associated with inflammatory dermatoses. Relative to normal human control skin, PPARγ transcripts in psoriatic and atopic lesions are reduced 8-and 3.3-fold, respectively [17]. Another study demonstrated that PPARG mRNA is significantly decreased in human lichen planopilaris, a form of scarring (cicatricial) alopecia [13].…”

Section: Introductionmentioning

confidence: 99%

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

Konger

Derr‐Yellin

Zimmers

et al. 2021

IJMS

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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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“…Another study confirmed the downregulation of PPARγ in explanted fibroblasts of lesional skin from patients with systemic sclerosis [ 98 ]. In addition, PPARγ has been reported to be downregulated in UV-irradiated damaged skin [ 185 ], in systemic lupus erythematosus patients with skin lesions [ 187 ] and in psoriatic and atopic lesions [ 186 ]. An investigation of 100 acne patients compared to 100 healthy subjects further found that the Pro12Ala polymorphism of the PPARγ gene, which results in decreased PPARγ transcriptional activity, is associated with a lower risk of acne vulgaris [ 196 ].…”

Section: The Endocannabinoid System In the Skinmentioning

confidence: 99%

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases

Ramer

Hinz

2022

Cells

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The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin’s immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.

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Estimation of peroxisome proliferators – activated receptor γ gene expression in inflammatory skin diseases: atopic dermatitis and psoriasis

Cited by 4 publications

References 34 publications

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

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

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases

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