RGD Reference Report - Inhibition of EP300 and DDR1 synergistically alleviates pulmonary fibrosis in vitro and in vivo. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Inhibition of EP300 and DDR1 synergistically alleviates pulmonary fibrosis in vitro and in vivo.

Authors: Tao, Jia  Zhang, Min  Wen, Zhijie  Wang, Baoxue  Zhang, Lei  Ou, Yu  Tang, Xu  Yu, Xiaoping  Jiang, Qinglin 
Citation: Tao J, etal., Biomed Pharmacother. 2018 Oct;106:1727-1733. doi: 10.1016/j.biopha.2018.07.132. Epub 2018 Jul 30.
RGD ID: 151347411
Pubmed: PMID:30119248   (View Abstract at PubMed)
DOI: DOI:10.1016/j.biopha.2018.07.132   (Journal Full-text)


OBJECTIVES: Pulmonary fibrosis is strongly correlated with inflammation factors, cytokine, and collagen secretion, whereby discoidin domain receptor 1 (DDR1) signaling plays an important role. EP300 is defined as an acetyltransferase that can acetylate histone and has been broadly studied in several chronic diseases, including cancer, inflammation and fibrosis. This study aimed to investigate the relationship between p300 and DDR1 in the pathological processes of pulmonary fibrosis.
MATERIALS AND METHODS: Transcriptome analysis of single cell RNA-sequencing for idiopathic pulmonary fibrosis (IPF) bronchial epithelial cells demonstrated that both DDR1 and EP300 were up-regulated and involved in the regulation of autophagy, cellular response to organonitrogen compounds, and collagen metabolic pathways, respectively. The anti-fibrotic and anti-inflammation effects of Pim1 and DDR1 inhibitors in bleomycin-induced IPF murine models were estimated.
RESULTS: We discovered that overexpression of EP300 signaling induced MRC5 human fibroblast cells that up-regulated the expression of DDR1 and FN1; however, no effects on COL1 A1 and DDR1 phosphorylation were observed. Mechanistically, TGF-β1 activated FN1, collagen, and DDR1 signaling could be reversed by the combination of p300 siRNA and DDR1 inhibitors. Moreover, the EP300 inhibitor SGC-CBP30 displayed synergistic effects with DDR1 inhibitors in pathogenic scores, airway goblet cell counts in bronchoalveolar lavage fluid (BALF), IL-4, IFN-γ, FN1COL1 A1 secretion and α-SMA, a marker of myofibroblast.
CONCLUSIONS: The EP300 siRNA and inhibitors sensitized DDR1 inhibitors in our pulmonary fibrosis models in vitro and in vivo, implicating a combined inhibition of DDR1 with EP300 as potential therapies for IPF.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DDR1Humanidiopathic pulmonary fibrosis treatmentISODdr1 (Rattus norvegicus) RGD 
DDR1Humanidiopathic pulmonary fibrosis  IEP mRNA:increased expression:lung (human)RGD 
Ddr1Ratidiopathic pulmonary fibrosis treatmentIMP  RGD 
Ddr1Ratidiopathic pulmonary fibrosis  ISODDR1 (Homo sapiens)mRNA:increased expression:lung (human)RGD 
Ddr1Mouseidiopathic pulmonary fibrosis treatmentISODdr1 (Rattus norvegicus) RGD 
Ddr1Mouseidiopathic pulmonary fibrosis  ISODDR1 (Homo sapiens)mRNA:increased expression:lung (human)RGD 
EP300Humanidiopathic pulmonary fibrosis treatmentISOEp300 (Rattus norvegicus) RGD 
EP300Humanidiopathic pulmonary fibrosis  IEP mRNA:increased expression:lung (human)RGD 
Ep300Ratidiopathic pulmonary fibrosis treatmentIMP  RGD 
Ep300Ratidiopathic pulmonary fibrosis  ISOEP300 (Homo sapiens)mRNA:increased expression:lung (human)RGD 
Ep300Mouseidiopathic pulmonary fibrosis treatmentISOEp300 (Rattus norvegicus) RGD 
Ep300Mouseidiopathic pulmonary fibrosis  ISOEP300 (Homo sapiens)mRNA:increased expression:lung (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ddr1  (discoidin domain receptor tyrosine kinase 1)
Ep300  (E1A binding protein p300)

Genes (Mus musculus)
Ddr1  (discoidin domain receptor family, member 1)
Ep300  (E1A binding protein p300)

Genes (Homo sapiens)
DDR1  (discoidin domain receptor tyrosine kinase 1)
EP300  (E1A binding protein p300)


Additional Information