{"doi":"10.1172/jci.insight.150887","title":"DDR1 contributes to kidney inflammation and fibrosis by promoting the phosphorylation of BCR and STAT3","abstract":"Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen, contributes to chronic kidney disease. However, its role in acute kidney injury and subsequent development of kidney fibrosis is not clear. Thus, we performed a model of severe ischemia/reperfusion-induced acute kidney injury that progressed to kidney fibrosis in WT and Ddr1-null mice. We showed that Ddr1-null mice had reduced acute tubular injury, inflammation, and tubulointerstitial fibrosis with overall decreased renal monocyte chemoattractant protein (MCP-1) levels and STAT3 activation. We identified breakpoint cluster region (BCR) protein as a phosphorylated target of DDR1 that controls MCP-1 production in renal proximal tubule epithelial cells. DDR1-induced BCR phosphorylation or BCR downregulation increased MCP-1 secretion, suggesting that BCR negatively regulates the levels of MCP-1. Mechanistically, phosphorylation or downregulation of BCR increased β-catenin activity and in turn MCP-1 production. Finally, we showed that DDR1-mediated STAT3 activation was required to stimulate the secretion of TGF-β. Thus, DDR1 contributes to acute and chronic kidney injury by regulating BCR and STAT3 phosphorylation and in turn the production of MCP-1 and TGF-β. These findings identify DDR1 an attractive therapeutic target for ameliorating both proinflammatory and profibrotic signaling in kidney disease.","journal":"JCI Insight","year":2021,"id":154336,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653921,"name":"Gema Bolás","orcid":"0000-0001-7809-1959","position":1,"is_corresponding":false},{"id":467199,"name":"Fabian Bock","orcid":"0000-0002-0788-2945","position":2,"is_corresponding":false},{"id":653922,"name":"Xiuqi Zhang","orcid":"0009-0008-8606-7105","position":3,"is_corresponding":false},{"id":654539,"name":"Favour C. Akabogu","orcid":null,"position":4,"is_corresponding":false},{"id":448126,"name":"Ming‐Zhi Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":653923,"name":"Mark de Caestecker","orcid":"0000-0002-5780-4216","position":6,"is_corresponding":false},{"id":653924,"name":"Min Yang","orcid":"0000-0002-0954-7227","position":7,"is_corresponding":false},{"id":340022,"name":"Haichun Yang","orcid":"0000-0003-4265-7492","position":8,"is_corresponding":false},{"id":241280,"name":"Ethan Lee","orcid":"0000-0001-8405-6156","position":9,"is_corresponding":false},{"id":321483,"name":"Leslie S. Gewin","orcid":"0000-0002-6146-1092","position":10,"is_corresponding":false},{"id":271631,"name":"Agnes B. Fogo","orcid":"0000-0003-3698-8527","position":11,"is_corresponding":false},{"id":276954,"name":"W. Hayes McDonald","orcid":"0000-0002-3510-426X","position":12,"is_corresponding":false},{"id":329060,"name":"Roy Zent","orcid":"0000-0003-2983-8133","position":13,"is_corresponding":false},{"id":506361,"name":"Ambra Pozzi","orcid":"0000-0001-8502-1481","position":14,"is_corresponding":false},{"id":653920,"name":"Corina M. Borza","orcid":"0000-0001-9113-110X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:43:49.684414Z","pmid":"34941574","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}