Comparing transcriptional profiles of skin biopsies from healthy controls and subjects with chronic pruritus of unknown origin and atopic dermatitis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237920 | GEO | 2023/07/21
REPOSITORIES: GEO
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Project description:Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and intense pruritus. Skin inflammation mediated by transient receptor potential vanillin 3 (TRPV3) in keratinocytes is a key mechanism driving the progression of AD. Paeonol is a bioactive phenolic compound extracted from the root bark of the Paeonia genus, which has demonstrated anti-inflammatory activities. Whether paeonol alleviates skin inflammation by inhibiting TRPV3 in the treatment of AD remains unclear.Objective: This study aims to investigate the therapeutic efficacy of paeonol against AD and its underlying anti-inflammatory mechanism.Methods: The therapeutic effects of paeonol were evaluated in a mouse model of AD induced by MC903 or carvacrol, as well as in tumor necrosis factor-alpha (TNF-α)-stimulated HaCaT cell line. Itch-related behaviors, hematoxylin-eosin (H&E) staining and toluidine blue staining were assessed in AD mice to evaluate the anti-atopic activity of paeonol. TRPV3 expression and function in keratinocytes were examined by Quantitative Real-time-PCR (qPCR), WB, immunofluorescence (IF) and Ca2+ imaging experiments. The anti-inflammation effect and its mechanisms of paeonol were measured by RNA sequencing (RNA-seq), H&E staining, qPCR and ELISA. Whole-cell patch-clamp were used to measure the excitability of trigeminal ganglion (TG) neurons treated by Chemokine (C-C motif) ligand 3 (CCL3).Results: Paeonol significantly alleviated MC903 and carvacrol-induced pruritus, epidermal hyperplasia and skin inflammation. Paeonol inhibited the expression and function of TRPV3 in keratinocytes, thereby inhibiting the activating of nuclear factor κB (NF-κB) pathway and reducing the secretion of CCL3. Downregulation of CCL3 expression in keratinocytes reduces the number of macrophages in the skin and inhibits their polarization to the M1 type. Moreover, paeonol also reversed the hyperexcitability of TG induced by increased CCL3, thus alleviated pruritus. Conclusion: Our study demonstrated that the activation of TRPV3 in keratinocytes aggravated skin inflammation and pruritus by promoting the secretion of CCL3. Paeonol alleviated AD by inhibiting the TRPV3/NF-κB/CCL3 axis in keratinocytes, thereby reducing macrophage-related skin inflammation, and inhibiting the hyperexcitability of TG neurons. These findings provide a novel therapeutic mechanism of paeonol in treating AD.
2025-12-01 | GSE289250 | GEO
Project description:Chronic pruritus is a pathological condition associated with numerous systemic, dermatologic, and neurologic disorders. Chronic pruritus of unknown origin (CPUO) represents a distinct clinical subtype characterized by persistent itch without an identifiable underlying cause. While emerging evidence implicates neuroimmune dysregulation in chronic pruritus, the specific mechanisms driving CPUO remain poorly understood. Objective: To characterize the neuroimmune mechanisms underlying CPUO, with a focus on identifying potential diagnostic markers. Single-cell RNA sequencing of peripheral blood cells from patients and healthy controls was conducted. Single-cell transcriptomic analysis revealed dysregulated monocytes and hyperactive natural killer (NK) cells overexpressing CCL3.
2025-11-21 | GSE295457 | GEO
Project description:Atopic dermatitis (AD) is a common pruritic dermatitis with macroscopically nonlesional skin that is often abnormal. Therefore, we used high-density oligonucleotide arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analyzed included normal skin from five healthy nonatopic adults and both minimally lesional skin and nearby or contralateral nonlesional skin from six adult AD patients. Keywords: disease state analysis We used high-density oligonucleotide Affymetrix Human U133A GeneChip arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analyzed included normal skin from five healthy nonatopic adults and both minimally lesional skin and nearby or contralateral nonlesional skin from six adult AD patients.
2006-10-01 | E-GEOD-5667 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD) is a common pruritic dermatitis with macroscopically nonlesional skin that is often abnormal. Therefore, we used high-density oligonucleotide arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analyzed included normal skin from five healthy nonatopic adults and both minimally lesional skin and nearby or contralateral nonlesional skin from six adult AD patients. Keywords: disease state analysis
2006-10-01 | GSE5667 | GEO
Project description:Uremic pruritus (UP) is one of the common symptoms in patients with uremia, and its etiology and mechanism have not been fully understood. In view of the high incidence of UP, finding the specific changed proteins in blood of UP patients will help revealing the potential biological mechanisms of UP and explore biomarkers. In this study, LC-MS/MS based data independent acquisition (DIA) mode was used to analyze the serum samples of 54 UP patients (DKD-UP, HN-UP and GN-UP, n=18 for each), 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD).
2024-03-08 | PXD045336 | Pride
Project description:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B–induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRb-/- or Rag1-/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FceRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD. A total of six samples were analyzed. Back skin samples from healthy or AD-induced C57BL/6, PLC-beta 3 KO (C57BL/6 background), and NC/Nga mice were collected for total RNA extraction. Pooled RNA from 2-4 mice per condition were used for analysis.
2013-12-10 | E-GEOD-53132 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD) is a pruritic and inflammatory disorder characterized by elevated levels of thymic stromal lymphopoietin (TSLP). Pruritus is prevalent in epidermolysis bullosa (EB). Currently, epidermal barrier disruption is known to trigger TSLP upregulation, however, mechanisms controlling TSLP expression remain incompletely understood. Tslp levels were highly upregulated in the epidermis and in the serum of keratin-deficient mice. Cultured keratinocytes either lacking keratins or expressing the dominant K14p.Arg131Pro show highly increased TSLP. Re-expression of wild-type K14 normalized TSLP levels. We demonstrate that keratins regulate Tslp expression in parts through MEK1/2 activation. The finding that 8 out of 17 EBS patients show elevated TSLP serum levels supports a major role of keratins in TSLP regulation. Our data identify a novel, keratin-dependent and cell-intrinsic regulation of Tslp. Elevated TSLP levels likely explain the high prevalence of pruritus in EBS and additional forms of EB, suggesting TSLP as novel biomarker for pruritus in EB. MEK1/2, in addition to calcineurin inhibitors, might be suitable drugs to treat itch in EB. Investigation was carried out using Keratin deficient keratinocytes isolated from typeI keratin mice.
2016-03-26 | E-GEOD-79596 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD) is the chronic inflammatory skin disease accompanied with severe pruritus. To explore the roles of EGR1 in atopic dermatitis and the relationship between EGR1 and pruritus-scratching behavior, we used a atopic dermatitis-like mouse model driven by house dust mite (HDM) treatment in wild type and EGR1 KO mice, followed with RNA-sequencing analysis.
2024-01-15 | GSE214750 | GEO
Project description:The aim of the study was to identify genes which are differentially expressed in the blood of dogs with canine atopic dermatitis (AD) in comparison to healthy control dogs. Diagnosis of AD was based on compatible history and clinical signs determined using Willemse and Prélaud diagnostic criteria, completed by Favrot criteria as follows: pruritus sine material, indoor lifestyle and the exclusion of other causes of pruritus ongoing for at least one year. Clinical diagnosis of atopic dermatitis was confirmed by serological allergy testing (IDEXX allergic panel test) and intradermal skin testing (Artuvetrin test set, Netherlands). In order to avoid the role of food antigens as a cause of the skin condition elimination diets was used for 6–8 weeks. No anti-inflammatory drugs were given for at least 3 weeks prior examination with serological test, intradermal test and blood collection. All dogs, which were classified to the investigated group had positive reactions in serological allergy testing and intradermal skin testing.
2016-08-31 | GSE76119 | GEO
Project description:Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Serum from 8 children with AD and 8 healthy children were collected
2014-10-17 | E-GEOD-62404 | biostudies-arrayexpress