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http://purl.uniprot.org/citations/36257259http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36257259http://www.w3.org/2000/01/rdf-schema#comment"

Background

Discoidin Domain Receptor1 (DDR1) is a member of receptor tyrosine kinases (RTKs) which have been reported to be associated with idiopathic pulmonary fibrosis (IPF), but the mechanism remains unclear.

Methods

Bleomycin-induced IPF mice model was performed in this study, and two DDR1 inhibitors were administered in vivo, to investigate the role of DDR1 in IPF. Lentivirus mediated DDR1-/- stable Raw264.7 macrophage cell line or DDR1 inhibitors treatment in vitro, to study the effect of DDR1 on inflammasome activation and macrophage responses. All of the mechanisms were further tested in the lung sections of IPF patients.

Result

Here, we reported that: (i) Both specific inhibitors of DDR1 dramatically alleviated the symptoms of bleomycin-induced IPF models. (ii) Immunofluorescence staining showed that DDR1 signaling is activated in macrophages. In vivo molecular biological analysis proved that DDR1 activation exacerbates IPF inflammation through inflammasome signaling, macrophage activation, and M1/M2 polarization. (iii) Extracellular matrix (ECM) such as Collagen 1 activates DDR1 in macrophage cell line Raw264.7 in vitro, to mediate inflammasome activation and macrophage responses. (iv) DDR1 activation in macrophage was confirmed in IPF patients' samples, which could be one of the mechanisms for the pathogenesis of IPF.

Discussion

In this study, we firstly reported DDR1 activation in macrophages to play a role in IPF via inflammasome activation and macrophage responses. In addition, DDR1 inhibitors DDR1-IN-1 and DDR1-IN-2 exerted significant anti-inflammatory and anti-fibrotic effects in IPF, all of which provide a potentially effective therapeutic medication for clinical IPF treatment."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.org/dc/terms/identifier"doi:10.1016/j.intimp.2022.109294"xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Chen Q."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Chen H."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Du Y."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Guan J."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Wang J."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Wen Y."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Xie S."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Yan J."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/author"Tao A."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/name"Int Immunopharmacol"xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/pages"109294"xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/title"DDR1 activation in macrophage promotes IPF by regulating NLRP3 inflammasome and macrophage reaction."xsd:string
http://purl.uniprot.org/citations/36257259http://purl.uniprot.org/core/volume"113"xsd:string
http://purl.uniprot.org/citations/36257259http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36257259
http://purl.uniprot.org/citations/36257259http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36257259
http://purl.uniprot.org/uniprot/#_O35407-mappedCitation-36257259http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36257259
http://purl.uniprot.org/uniprot/#_Q03146-mappedCitation-36257259http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36257259
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