Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-inflammatory effects of differential molecular weight hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation

ABSTRACT: Background: The biological functions of HA are related to its molecular weight and binding to its receptor TLR4 or CD44. Recent studies have shown that LMW-HA exhibits proinflammatory effects, while HMW-HA functions as an anti-inflammatory factor. UVB-induced epidermal inflammation is mainly mediated by endogenous molecules, such as DAMPs, that cause severe skin damage by activating TLR signaling pathways. Objective: Since both LMW- and HMW-HA have inhibitory functions on TLR-mediated macrophage inflammation, HA is assumed to suppress UVB-induced DAMP-mediated inflammation in the skin. In this study, both uLMW-HA and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation. Methods: To elucidate whether HAs have anti-inflammatory effects on inflammation induced by UVB exposure, we performed whole transcriptome analysis in HaCaT cells treated with or without HAs after UVB exposure. Results: UV radiation induced upregulation or downregulation of genes (FC>1.2 or FC<0.8, q<0.05) were obtained. We analyzed network of these genes with Ingenuity Pathway analysis using information collected from databases on protein interactions. IL-6 was detected as an upstream factor of HA suppressing UV-radiation effects on HaCaT cells. Canonical pathway analysis also shows uLMW-HA downregulated NF-κB, which is located downstream of TLR4 signaling pathway, although HMW-HA did not show downregulation of NF-κB signaling pathway. Conclusions: Both uLMW-HA and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201850 | GEO | 2022/08/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The impact of low molecular weight hyaluronan on the lipidomic profile and global gene expression of peripheral blood mononuclear cells in asthma

Project description:Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix involved in the pathogenesis of asthma and other chronic inflammatory diseases. During inflammation there is an increased breakdown of HA, resulting in the local and systemic accumulation of low molecular weight (LMW) HA. Eicosanoids, derived from cytosolic phospholipase A2 group IVA activation, are potent lipid mediators also attributed to acute and chronic inflammation. We investigated the effect of LMW HA on lipidomic profile and global gene expression in PBMCs of patients with mild-to-moderate and severe asthma. We found that LMW HA increased production of 68 unique lipid species, among which PGE2, PGA2, PGD2, PGF2a, 15-HETE, TxB2, 11,12-EET, 14,15 EET, 13-HOTrE(y) and 16 (17) EpDPE were significantly upregulated in severe asthmatics. We also performed a systematic genome-wide expression analysis of LMW HA signaling, confirming its highly immunostimulatory potential. However, in severe asthmatics the LMW HA-induced global gene expression profile showed a comprehensive impairment in interferon signaling, cell apoptosis and cell movement, leading to diminished antiviral responses. Likewise, LMW HA-induced production of IL12 p40, CXCL10, CXCL11 and CCL8was markedly reduced in severe asthmatics. Our findings suggest a previously unforeseen link between extracellular matrix, global lipid production and antiviral responses in the pathogenesis of severe asthma. We used microarray to perform a systematic genome-wide expression analysis of LMW HA effect in peripheral blood mononuclear cells in control subjects, mild-to moderate asthma and severe asthma patients

2016-11-14 | GSE59019 | GEO

Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan

2023-09-08 | GSE234154 | GEO

Increased hyaluronan by naked mole-rat HAS2 improves healthspan in mice [microbiome]

2023-06-12 | GSE234286 | GEO

Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

2023-08-10 | GSE234563 | GEO

The distribution of individual miRNA species between high-molecular weight and low-molecular weight RISC complexes by small RNA sequencing in thyroid cancer cell lines

Project description:Thyroid cancer is the most prevalent malignancy of the endocrine system. We and others have shown that several microRNAs, which are ~21-24nt post-transcriptional gene regulators, are aberrantly expressed in anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) tissues and cell lines. In the cell, miRNAs are bound to Argonaute (AGO) proteins as low molecular weight RNA Induced Silencing Complexes (LMW-RISCs) that can then assemble into high molecular weight RISCs (HMW-RISCs) that also include additional proteins and mRNA. In this study, we sought to analyze the association of miRNAs across RISC complexity in ATC and PTC. For both ATC and PTC lines, miRNAs were enriched in HMW-RISC and LMW-RISC fractions compared with intermediate fractions or very low molecular weight (AGO-poor) fractions. Furthermore, 60% of all miRNAs were more abundant in LMW-RISC versus HMW- RISC fractions by ~2-4 fold. Surprisingly, miR-21-5p, one of the most abundant miRNAs in both ATC and PTC lines, was consistently one the least abundant miRNAs in HMW-RISC and the most enriched miRNA in LMW-RISC fractions. These findings suggest that miR-21 may be uniquely distributed in RISCs relative to other miRNAs. Furthermore, the methodology described here is a useful way to assess the relative magnitude of miR-21association with HMW and LMW-RISCs and may help to reveal the true roles of this miRNA in thyroid cancer development, progression, and treatment.

2020-02-28 | GSE146015 | GEO

The miRNA microarray data after UVB exposure to human keratinocyte HaCaT cells

Project description:UVB plays a key role in inflammation and DNA damage in human skin. Human keratinocyte HaCaT cells were utilized to determine the up- and down-regulated miRNA after UVB exposure. We used microarrays to identify the miRNA affected after UVB (15 mJ/cm^2) exposure to HaCaT cells

2020-03-23 | GSE142534 | GEO

Ultraviolet light induces HERV expression to activate RIG-I signaling pathway in keratinocytes

Project description:Skin inflammation and photosensitivity are common in lupus erythematosus (LE) patients, and Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) patients. Type I interferons (IFN) are upregulated in LE skin after UV exposure, however, the mechanisms to explain UVB-induced inflammation remain unclear. Here we performed RNA-seq to HaCat cells with UVB irradiation to characterize gene expression and resolve differential responses of keratinocytes, in order to understand how the keratinocyte response contributes to the disease. Our data showed that HERVs and RIG-I pathway were activated in keratinocytes after UVB exposure and indicate that RIG-I pathway and HERVs are involved in proinflammatory by activating the I-IFN pathway, which provide a novel insight into how UVB promotes and aggravate skin lesion of LE patients.

2022-05-01 | GSE198792 | GEO

Blocking hyaluronan synthesis alleviates acute lung allograft rejection.

Project description:Lung allograft rejection results in the accumulation of low molecular weight hyaluronic acid (LMW-HA), which further propagates inflammation and tissue injury. We have previously shown that therapeutic lymphangiogenesis in a murine model of lung allograft rejection reduced tissue LMW-HA and was associated with improved transplant outcomes. Herein we investigated the use of 4-Methylumbelliferone (4-MU), a known inhibitor of HA synthesis, to alleviate acute allograft rejection in a murine model of lung transplantation. We found that treating mice with 4-MU from day 20-30 post-transplant was sufficient to significantly improve outcomes, characterized by a reduction in T-cell mediated lung inflammation, LMW-HA content and improved pathology scores. In vitro, 4-MU directly attenuated activation, proliferation, and differentiation of naïve CD4+ T-cells into Th1 cells. As 4-MU has already been demonstrated to be safe for human use, we believe examining 4-MU for the treatment of acute lung allograft rejection may be of clinical significance.

2021-12-15 | GSE183142 | GEO

Gene signature profiles in lung tissues of wild type mice or Has2 heterozygous deficient mice stimulated chronically with ovalbumin

Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2), which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified HAS2 as a candidate gene for susceptibility to adult asthma. However, little is known if HAS2 dysfunction affects airway remodeling and steroid insensivity. In this study, we clarified the dysfunction of Has2 triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. Methods: Ovalbumin (OVA) was used to induce eosinophilic airway inflammation and airway remodeling in Has2 heterozygous deficient (Has2+/−) mice and their wild-type (WT) littermates. Lung tissue histology, bronchoalveolar lavage fluid cell counting, quantitative PCR, HA size analysis, multiplex cytokines and chemokines analysis, RNA sequencing, anti IL-17 neutralization experiment were performed. Results: After chronic OVA stimulation, Has2+/− (Has2+/--OVA) mice showed significant decrease of Has2 mRNA expression levels, HMW-HA, HA-binding protein, and TGF-β. Has2+/--OVA mice demonstrated increased eosinophilic airway inflammation, goblet cell hyperplasia, and IL-17 levels. RNA sequencing demonstrated downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in Has2+/--OVA mice. Combined treatment with anti IL-17 antibody and dexamethasone reduce steroid insensitivity in Has2+/--OVA mice Conclusions: Has2 attenuation worsen eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. This severe intractable phenotype might be induced by impairment of TGF-β signaling and ER stress response related signaling. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling, and could potentially be exploited for therapeutic benefit to asthma patients.

2022-01-26 | GSE181966 | GEO

Small RNA discovery in developing mouse and during human in vitro beta-cell differentiation protocol

Project description:The aim of this experiment was to identify novel, small (<600bp), capped, polyA-tailed RNA transcripts in mouse E14.5 pancreas, liver, and brain and at stages S1, S2, S3 within our human in vitro beta-cell differentiation protocol. Low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions were separated.

2015-04-02 | E-MTAB-3489 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data