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Highly concentrated trehalose prevents IL-4/IL-13-induced skin barrier impairment by suppressing IL-33 expression and increasing Nrf2 activation in epidermal keartinocytes

ABSTRACT: Highly concentrated trehalose prevents IL-4/IL-13-induced skin barrier impairment by suppressing IL-33 expression and increasing Nrf2 activation in epidermal keartinocytes

PROVIDER: PRJNA1024469 | ENA |

REPOSITORIES: ENA

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Highly concentrated trehalose prevents IL-4/IL-13-induced skin barrier impairment by suppressing IL-33 expression and increasing Nrf2 activation in epidermal keartinocytes

Project description:Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis (AD). In high concentrations, the nonreducing disaccharide α-d-glucopyranosyl α-d-glucopyranoside (trehalose) can induce transient senescence-like state in fibroblasts and promote wound repair. Here we have investigated the direct effect of a high concentration of trehalose on primary human keratinocytes (KCs) and demonstrated its specific role in the skin barrier. RNA-seq analysis revealed that trehalose regulates many skin-barrier-associated genes in T helper 2 (Th2) cytokines interleukin (IL)-4/IL-13-treated and -untreated KCs. Using monolayer-cultured post-confluent normal human KCs and living skin equivalent (LSE), we identified IL-4/IL-13-downregulated differentiation markers and various epidermal antimicrobial proteins, all of which were significantly upregulated or restored by trehalose (60 mg/mL). Trehalose inhibited IL-33 expression and reduced nuclear IL-33 by activating MEK5- extracellular signal-regulated kinase (ERK)-5 and suppressing MEK1/2-ERK pathways. It also increased nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase 1 (HMOX1) activation via c-Jun N-terminal kinase (JNK), thus, neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription (STAT)3 and STAT6 activation and restored various skin barrier molecules reduced by IL-4/IL-13 via IL-33 downregulation and Nrf2-HMOX1 activation. This study demonstrates that trehalose might play salubrious roles as skin barrier repair in AD.

2024-09-30 | GSE244738 | GEO

Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21

Project description:Trehalose is the nonreducing disaccharide of glucose, evolutionarily conserved in invertebrates. The living skin equivalent (LSE) is an organotypic coculture containing keratinocytes cultivated on fibroblast-populated dermal substitutes. We demonstrated that human primary fibroblasts treated with highly concentrated trehalose promote significantly extensive spread of the epidermal layer of LSE without any deleterious effects. The RNA-seq analysis of trehalose-treated 2D and 3D fibroblasts at early time points revealed the involvement of the CDKN1A pathway, the knockdown of which significantly suppressed the upregulation of DPT, ANGPT2, VEGFA, EREG, and FGF2. The trehalose-treated fibroblasts were positive for senescence-associated β-galactosidase. Finally, transplantation of the dermal substitute with trehalose-treated fibroblasts accelerated wound closure and increased capillary formation significantly in the experimental mouse wounds in vivo, which was canceled by the CDKN1A knockdown. These data indicate that high-concentration trehalose can induce the senescence-like state in fibroblasts via CDKN1A/p21, which may be therapeutically useful for optimal wound repair.

2023-01-10 | GSE184892 | GEO

Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21

Project description:Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21

| PRJNA766853 | ENA

The consequences of trehalose intake on brain metabolism in mice

Project description:In the present study, we investigated the consequences of trehalose intake on brain metabolism in mice drinking for 0, 1, and 10 days. Microarray analyses were performed to identify the molecular targets involved in the brain metabolism of trehalose intake.

2019-04-01 | GSE112976 | GEO

Commercial bacterial culture concentrated starter "Profiline"

Project description:Commercial bacterial culture concentrated starter "Profiline" Metagenome

| PRJNA900167 | ENA

Stress profile elicited by trehalose-6-phosphate accumulation in Mycobacterium tuberculosis

Project description:The otsB2 gene encoding trehalose-6-phosphate phosphatase is essential for in vitro growth of Mycobacterium tuberculosis and required to establish an acute infection in mice. Essentiality of otsB2 is due to direct or indirect toxic effects associated with the substrate trehalose-6-phosphate that accumulates when OtsB2 gene expression is impaired. In order to gain insight into the molecular basis of trehalose-6-phosphate mediated toxic effects, whole genome transcriptome profiling was done using RNA-seq. A conditional otsB2 mutant of Mycobacterium tuberculosis was generated by inserting an anhydrotetracycline-inducible promoter cassette upstream of the otsB2 start codon,and the transcriptome profile of a fully induced mutant resembling the wildtype phenotype was compared to that of a partially silenced mutant under conditions where 30% residual growth relative to the fully induced mutant was observed.

2016-11-21 | GSE70291 | GEO

Transcriptomic RNA-sequencing analysis of the hypervirulent Clostridioides difficile R20291 strain in response to trehalose

Project description:Clostridioides difficile, the leading cause of antibiotic-associated diarrhoea worldwide, is a genetically diverse species which can metabolise a number of nutrient sources upon colonising a dysbiotic gut environment. Trehalose, a disaccharide sugar consisting of two glucose molecules bonded by an α 1,1-glycosidic bond, has been hypothesised to be involved in the emergence of C. difficile hypervirulence due to its increased utilisation by the RT027 and RT078 strains. Using RNA-sequencing analysis, we report the identification of a putative trehalose metabolism pathway which is induced during growth in trehalose: this has not been previously described within the C. difficile species. These data demonstrate the metabolic diversity exhibited by C. difficile which warrants further investigation to elucidate the molecular basis of trehalose metabolism within this important gut pathogen.

2023-05-26 | GSE232033 | GEO

ApoE-knockout mice liver on high fat diet treated with trehalose or agmatine.

Project description:ApoE-knockout mice liver on high fat diet developing liver steatosis were treated with trehalose or agmatine for 16 weeks.

2024-08-10 | PXD049421 | Pride

Clinical trial for the comparison between low and high concentrated Injection Solution Ability for Colorectal endoscopic submucosal dissection: ISAC study

Project description:Interventions: high-concentrated injection solution low-concentrated injection solution Primary outcome(s): The inferiority of ESD procedure time between high-concentrated and low-cencetrated injection solution Study Design: Parallel Randomized

| 34494 | ecrin-mdr-crc

Genome-wide analysis of trehalose-responsive gene expression in control or JNCL human fibroblasts.

Project description:Analysis of changes in gene expression induced by trehalose administration in fibroblasts derived from JNCL patients and control fibroblasts.

2016-12-13 | GSE76643 | GEO

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