Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chitinase 1: A novel therapeutic target in metabolic dysfunction-associated steatohepatitis

ABSTRACT: Chitinase 1: A novel therapeutic target in metabolic dysfunction-associated steatohepatitis

PROVIDER: PRJNA1124123 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR29418921.fastq.gz	Fastqsanger.gz
	SRR29418922.fastq.gz	Fastqsanger.gz
	SRR29418923.fastq.gz	Fastqsanger.gz
	SRR29418924.fastq.gz	Fastqsanger.gz
	SRR29418925.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 19

Similar Datasets

Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis.

Project description:BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis.MethodsFibrotic liver tissue and serum from distinct patient groups were analyzed using nCounter MAX, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor. Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry.ResultsCHIT1 expression in fibrotic liver tissues was significantly correlated with the extent of liver fibrosis, macrophages, and inflammation. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice. Treatment with OATD-01 reduced non-alcoholic fatty liver disease activity score and Sirius red-positive area. Additionally, OATD-01-treated mice had lower CHIT1, F4/80, and α-smooth muscle actin positivity, as well as significantly lower levels of inflammatory markers, pro-fibrotic genes, and matrix remodeling-related mRNAs than vehicle-treated mice. Although the population of F4/80+CD11b+ intrahepatic mononuclear phagocytes remained unchanged, their infiltration and activation (CHIT1+MerTK+) significantly decreased in OATD-01-treated mice, compared with that observed in vehicle-treated mice.ConclusionsOur study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis.

| S-EPMC11459552 | biostudies-literature

Chitinase 1: A novel therapeutic target in metabolic dysfunction-associated steatohepatitis

Project description:Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice.

2024-10-16 | GSE269924 | GEO

Pneumosepsis survival in the setting of obesity leads to persistent steatohepatitis and metabolic dysfunction.

Project description:Pneumosepsis survival in the setting of obesity leads to persistent steatohepatitis and metabolic dysfunction.

2023-05-02 | GSE231504 | GEO

Silencing of S100A11 Attenuates Murine Metabolic Dysfunction-associated Steatohepatitis

Project description:Silencing of S100A11 Attenuates Murine Metabolic Dysfunction-associated Steatohepatitis

| PRJNA1300449 | ENA

Liver and Pancreatic-Targeted Interleukin-22 as a Therapeutic for Metabolic Dysfunction-Associated Steatohepatitis

Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutics. Previous research has shown that interleukin-22 (IL-22) can suppress beta-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. 10-fold lower doses of these bispecific biologics exceeded the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restored glycemic control, markedly reduced hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

2024-04-07 | MSV000094483 | MassIVE

Potential utility of L-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis

Project description:We examined the potential utility of L-carnitine for alleviating metabolic dysfunction-associated steatohepatitis (MASH) and preventing the development of hepatocellular carcinoma. Short-term L-carnitine administration ameliorated MASH through its anti-inflammatory effects.

2024-04-24 | GSE261938 | GEO

Hepatoprotective effect of cinnabarinic acid in metabolic dysfunction-associated steatohepatitis

Project description:Hepatoprotective effect of cinnabarinic acid in metabolic dysfunction-associated steatohepatitis

| PRJNA1162523 | ENA

Epithelial regeneration is modulated by chitin and chitinase activity

Project description:Epithelial injury underlies fibrotic and inflammatory lung diseases during which regenerative responses become dysregulated or recurrently engaged. Although environmental exposures are risk factors for severe lung disease, specific drivers of persistent epithelial and immune dysfunction are poorly understood. Here we identify a feedback circuit triggered by chitin, a common component of airborne particulate matter, that impacts lung health and regeneration after epithelial injury. In mice, damage to epithelial cells results in loss of homeostatic lung chitinase activity and accumulation of environmental chitin substrates; these disturbances impair epithelial renewal and drive activation of group 2 innate lymphoid cells (ILC2s). ILC2s, in turn, restore chitinase activity by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells, thereby promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear airway chitin and exhibit exacerbated inflammation, impaired epithelial regeneration, and increased mortality following epithelial injury. These effects are ameliorated by chitinase replacement therapy or AMCase overexpression, demonstrating that chitin degradation is crucial for restoring lung homeostasis after perturbation. The ILC2-chitinase response circuit thus comprises a tissue adaptation to a widespread environmental constituent and may be a target for alleviating persistent post-injury lung epithelial and immune dysfunction.

2024-12-31 | GSE275319 | GEO

Epithelial regeneration is modulated by chitin and chitinase activity

2024-12-31 | GSE275075 | GEO

Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S- producing enzymes altering persulfidome composition

Project description:Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive disease driven byobesity-related hepatic inflammation and oxidative stress. Recently, cysteine persulfidation (PSSH), a protective post-translational modification by hydrogen sulfide (H2S), was established to play a role in redox regulation. Despite the role of the liver in H2S metabolism, the function of PSSH in MASH remains underexplored. We demonstrated that H2S-producingenzymes are downregulated in both human and mouse livers with steatosis and fibrosis, resulting in a decline in global PSSH levels. Surprisingly, dimedone-switch mass spectrometry in dietary mouse models of distinct obesity-associated liver disease stages revealed dysregulated PSSH on specific proteins. In particular, increased hepatic PSSH levels of proteintyrosine phosphatases and redox regulators were found in advanced disease stages, suggesting a targeted adaptive response to oxidative stress. Overall, our findings demonstrated that impaired H2S production disrupts protective PSSH networks in MASH. However, selective PSSH preservation on redox-sensitive proteins may represent a compensatory mechanism, underscoring the therapeutic potential of persulfidation in restoring redox homeostasis during obesity-associated chronic liver disease.

2025-09-15 | PXD066952 | Pride

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