{"doi":"10.17615/k3hf-vf83","title":"NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis","abstract":"Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II–induced effects in hepatic stellate cells (HSCs), a fibrogenic cell type. Human HSCs express mRNAs of key components of nonphagocytic NADPH oxidase. Ang II phosphorylated p47phox, a regulatory subunit of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase activity. Ang II phosphorylated AKT and MAPKs and increased AP-1 DNA binding in a redox-sensitive manner. Ang II stimulated DNA synthesis, cell migration, procollagen α1(I) mRNA expression, and secretion of TGF-β1 and inflammatory cytokines. These effects were attenuated by N-acetylcysteine and diphenylene iodonium, an NADPH oxidase inhibitor. Moreover, Ang II induced upregulation of genes potentially involved in hepatic wound-healing response in a redox-sensitive manner, as assessed by microarray analysis. HSCs isolated from p47phox–/– mice displayed a blunted response to Ang II compared with WT cells. We also assessed the role of NADPH oxidase in experimental liver fibrosis. After bile duct ligation, p47phox–/– mice showed attenuated liver injury and fibrosis compared with WT counterparts. Moreover, expression of smooth muscle α-actin and expression of TGF-β1 were reduced in p47phox–/– mice. Thus, NADPH oxidase mediates the actions of Ang II on HSCs and plays a critical role in liver fibrogenesis.","journal":"UNC Libraries","year":2020,"id":135143,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"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":232503,"name":"David A. Brenner","orcid":"0000-0003-2573-525X","position":1,"is_corresponding":false},{"id":591872,"name":"You-kyung Choi","orcid":"0000-0002-5146-6121","position":2,"is_corresponding":false},{"id":298735,"name":"Ramón Bataller","orcid":"0000-0002-1119-7799","position":3,"is_corresponding":false},{"id":592431,"name":"Jeffrey N. Lindquist","orcid":null,"position":4,"is_corresponding":false},{"id":342793,"name":"John J. Lemasters","orcid":"0000-0002-7627-6295","position":5,"is_corresponding":false},{"id":393860,"name":"Robert Schoonhoven","orcid":null,"position":6,"is_corresponding":false},{"id":592432,"name":"Yong Han Paik","orcid":null,"position":7,"is_corresponding":false},{"id":109692,"name":"Robert F. Schwabe","orcid":"0000-0003-4571-2098","position":8,"is_corresponding":false},{"id":591873,"name":"Yang Liu","orcid":"0000-0002-0712-9750","position":9,"is_corresponding":false},{"id":69803,"name":"Curt H. Hagedorn","orcid":null,"position":10,"is_corresponding":false},{"id":537959,"name":"Ting Qian","orcid":"0009-0009-4479-3376","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:31.787520Z","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":[]}