Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis

ABSTRACT: Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis

PROVIDER: PRJNA883744 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR21691604_1.fastq.gz	Fastqsanger.gz
	SRR21691604_2.fastq.gz	Fastqsanger.gz
	SRR21691605_1.fastq.gz	Fastqsanger.gz
	SRR21691605_2.fastq.gz	Fastqsanger.gz
	SRR21691606.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 21

Similar Datasets

Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis

Project description:Immune cells are fundamental regulators of extracellular matrix (ECM) production by fibroblasts and have important roles in determining extent of fibrosis in response to inflammation. Although much is known about fibroblast signaling in fibrosis, the molecular signals between immune cells and fibroblasts that drive its persistence are poorly understood. We therefore analyzed skin and lung samples of patients with diffuse cutaneous systemic sclerosis, an autoimmune disease that causes debilitating fibrosis of the skin and internal organs. Here we define a critical role of epiregulin – EGFR signaling between dendritic cells and fibroblasts to maintain elevated ECM production and accumulation in fibrotic tissue. Mechanistic studies demonstrate that epiregulin expression marks an inducible state of DC3 dendritic cells triggered by type I interferon. DC3-derived epiregulin activates EGFR on fibroblasts, which drives a positive feedback loop through NOTCH signaling. In well-established mouse models of skin and lung fibrosis, epiregulin was essential for persistence of fibrosis in both tissues, which could be abrogated by epiregulin genetic deficiency or a neutralizing antibody. Notably, therapeutic administration of epiregulin antibody reversed fibrosis in patient skin and lung explants, identifying it as a novel biologic drug target. Our findings reveal epiregulin as a crucial immune signal that maintains skin and lung fibrosis in multiple diseases and is a highly promising antifibrotic target.

2022-12-09 | GSE214088 | GEO

Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis.

Project description:Immune cells are fundamental regulators of extracellular matrix (ECM) production by fibroblasts and have important roles in determining extent of fibrosis in response to inflammation. Although much is known about fibroblast signaling in fibrosis, the molecular signals between immune cells and fibroblasts that drive its persistence are poorly understood. We therefore analyzed skin and lung samples of patients with diffuse cutaneous systemic sclerosis, an autoimmune disease that causes debilitating fibrosis of the skin and internal organs. Here, we define a critical role of epiregulin-EGFR signaling between dendritic cells and fibroblasts to maintain elevated ECM production and accumulation in fibrotic tissue. We found that epiregulin expression marks an inducible state of DC3 dendritic cells triggered by type I interferon and that DC3-derived epiregulin activates EGFR on fibroblasts, driving a positive feedback loop through NOTCH signaling. In mouse models of skin and lung fibrosis, epiregulin was essential for persistence of fibrosis in both tissues, which could be abrogated by epiregulin genetic deficiency or a neutralizing antibody. Therapeutic administration of epiregulin antibody reversed fibrosis in patient skin and lung explants, identifying it as a previously unexplored biologic drug target. Our findings reveal epiregulin as a crucial immune signal that maintains skin and lung fibrosis in multiple diseases and represents a promising antifibrotic target.

| S-EPMC9840167 | biostudies-literature

Effect of DNA damage on ligand stimulated EGFR signaling pathways

Project description:Effect of DNA damage on ligand stimulated EGFR signaling pathways

| PRJNA759859 | ENA

Angiogenin/ribonuclease 5 is an EGFR ligand and a serum biomarker for erlotinib sensitivity in pancreatic cancer

Project description:Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin/ANG) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a previously unrecognized role of ANG as a serum biomarker, which may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.

2018-04-18 | GSE109427 | GEO

Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype

Project description:Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype

| PRJNA791915 | ENA

Time-resolved proximity labeling of protein networks associated with ligand-activated EGFR

Project description:Ligand binding to the EGF receptor (EGFR) initiates signal transduction and endocytosis of the receptor. The mechanisms of endocytosis and regulation of signaling by endocytosis are poorly understood. Here, we combined peroxidase-catalyzed proximity labeling, isobaric peptide tagging and quantitative mass-spectrometry to define the dynamics of the proximity proteome of EGFR in response to ligand activation. Using this approach, we identified a network of signaling proteins, which remain associated with the receptor during its endocytosis and trafficking through the endosomal system. We showed that Trk-fused gene (TFG), a protein known to function at the endoplasmic reticulum exit sites, was enriched early/sorting endosome proximity proteome of EGFR and localized in early an sorting endosomes, and demonstrated that TFG regulates endosomal sorting of EGFR. This study provides a large-scale resource of time-dependent nanoscale environment of activated EGFR, thus opening avenues to discovering new regulatory mechanisms of membrane trafficking of receptor tyrosine kinases. EGFR-APEX2 Experiment Datasets: TMT 1-3: HEK293T cells (0, 1, 10, 30 and 60 minutes EGF treatment) TMT 4: HCT116 cells (0, 2, 4, 6 , 8 and 10 minutes EGF treatment) TMT 5: HEK293T cells (0, 2, 4, 6 , 8 and 10 minutes EGF treatment) TMT 6: HEK293T cells (0 and 10 minutes EGF treatment) TMT 7: HCT116 cells (0 and 10 minutes EGF treatment)

2022-06-04 | PXD030072 | Pride

ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion

Project description:ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion

| PRJNA875032 | ENA

E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding

Project description:E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding

| PRJNA1228921 | ENA

Selection for ligand-independent EGFR activation

Project description:Selection of activating EGFR mutations from randomly mutated EGFR libraries

| PRJEB49811 | ENA

E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding

Project description:The behavior of cells is governed by signals originating from their local environment, including mechanical forces that cells experience. Forces are transduced by mechanosensitive proteins, which can impinge on signaling cascades that are also activated by growth factor receptors upon ligand binding. However, the interplay between these mechanical and biochemical signals in the regulation of intracellular signaling networks remains incompletely understood. To elucidate this mechanochemical crosstalk, we conducted phosphoproteomic and transcriptomic analyses on epithelial monolayers subjected to mechanical strain. This approach revealed ERK signaling as a predominant strain-activated hub, initiated at the level of the upstream EGF receptor. Strain-induced EGFR/ERK signaling relies on mechanosensitive E-cadherin adhesions, as this signaling is disrupted upon genetic modulation of force transduction by the E-cadherin complex. Proximity labeling identified a connection between E-cadherin and ADAM17, an enzyme that mediates the shedding of soluble EGFR ligands. We developed a novel ADAM activity probe to demonstrate that mechanical strain induces ADAM activation, which relays mechanosensitive signaling from E-cadherin adhesions towards EGFR/ERK. Collectively, our data demonstrate how mechanical strain transduced by E-cadherin adhesion modulates the presence of EGFR ligands to regulate downstream ERK activity. Our findings illustrate how mechanical signals and biochemical ligands can operate within a single, linear signaling cascade.

2025-05-21 | GSE290599 | GEO

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