{"doi":"10.17615/6xkm-7p55","title":"Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis","abstract":"Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.","journal":"UNC Libraries","year":2020,"id":116045,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":375752,"name":"Hyungsuk Kim","orcid":"0000-0003-3919-4597","position":1,"is_corresponding":false},{"id":542886,"name":"Samantha Gould","orcid":"0009-0009-7685-4129","position":2,"is_corresponding":false},{"id":237302,"name":"Laura Barisoni","orcid":"0000-0003-0848-9683","position":3,"is_corresponding":false},{"id":392718,"name":"David S. Pisetsky","orcid":"0000-0002-3539-5351","position":4,"is_corresponding":false},{"id":542887,"name":"Thomas M. Coffman","orcid":"0000-0002-8433-1629","position":5,"is_corresponding":false},{"id":543657,"name":"Trinh T. Tran","orcid":null,"position":6,"is_corresponding":false},{"id":245997,"name":"Marie Jeansson","orcid":"0000-0003-1075-8563","position":7,"is_corresponding":false},{"id":543658,"name":"Minolfa C. Prieto‐Carrasquero","orcid":null,"position":8,"is_corresponding":false},{"id":542888,"name":"Mary H. Foster","orcid":"0000-0002-2555-4654","position":9,"is_corresponding":false},{"id":542889,"name":"Phillip Ruiz","orcid":"0000-0003-2291-4594","position":10,"is_corresponding":false},{"id":542890,"name":"Kelly Parsons","orcid":"0000-0002-6473-210X","position":11,"is_corresponding":false},{"id":542891,"name":"Benny J. Chen","orcid":"0000-0003-4588-3890","position":12,"is_corresponding":false},{"id":543659,"name":"Carie Facemire","orcid":null,"position":13,"is_corresponding":false},{"id":303482,"name":"Steven D. Crowley","orcid":null,"position":14,"is_corresponding":false},{"id":543660,"name":"A. Kathy Pazmino","orcid":null,"position":15,"is_corresponding":false},{"id":543656,"name":"Matthew P. Vasievich","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:40.596604Z","pmid":null,"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":[]}