{"doi":"10.1073/pnas.0908268106","title":"Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase","abstract":"<jats:p>\n                    Great arteries, as well as lungs and skin, contain elastic fibers as important components to maintain their physiological functions. Although recent studies have revealed that a glycoprotein fibulin-4 (FBLN4) is indispensable for the assembly of mature elastic fibers, it remains to be elucidated how FBLN4 takes part in elastogenesis. Here, we report a dose-dependent requirement for FBLN4 in the development of the elastic fibers in arteries, and a specific role of FBLN4 in recruiting the elastin-cross-linking enzyme, lysyl oxidase (LOX). Reduced expression of\n                    <jats:italic>Fbln4</jats:italic>\n                    , which was achieved with a smooth muscle-specific Cre-mediated gene deletion, caused arterial stiffness. Electron-microscopic examination revealed disorganized thick elastic laminae with aberrant deposition of elastin. Aneurysmal dilation of the ascending aorta was found when the\n                    <jats:italic>Fbln4</jats:italic>\n                    expression level was reduced to an even lower level, whereas systemic\n                    <jats:italic>Fbln4</jats:italic>\n                    null mice died perinatally from rupture of the diaphragm. We also found a specific interaction between FBLN4 and the propeptide of LOX, which efficiently promotes assembly of LOX onto tropoelastin. These data suggest a mechanism of elastogenesis, in which a sufficient amount of FBLN4 is essential for tethering LOX to tropoelastin to facilitate cross-linking.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2009,"id":631327,"datarank":0.7584368708022463,"base_score":5.056245805348308,"endowment":5.056245805348308,"self_citation_contribution":0.7584368708022463,"citation_network_contribution":0.0,"self_endowment_contribution":0.7584368708022463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":156,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1636029,"name":"Tadashi Inoue","orcid":null,"position":1,"is_corresponding":false},{"id":1636030,"name":"Tetsuya Ohbayashi","orcid":null,"position":2,"is_corresponding":false},{"id":1262119,"name":"Maretoshi Hirai","orcid":"0000-0001-6913-8655","position":3,"is_corresponding":false},{"id":329480,"name":"Kazuo Noda","orcid":"0000-0002-6024-0888","position":4,"is_corresponding":false},{"id":1636031,"name":"Lihua Y. Marmorstein","orcid":null,"position":5,"is_corresponding":false},{"id":527225,"name":"Daisuke Yabe","orcid":"0000-0002-5334-7687","position":6,"is_corresponding":false},{"id":1636032,"name":"Kyoko Takagi","orcid":null,"position":7,"is_corresponding":false},{"id":187068,"name":"Tomoya O. Akama","orcid":null,"position":8,"is_corresponding":false},{"id":1587353,"name":"Toru Kita","orcid":null,"position":9,"is_corresponding":false},{"id":1218368,"name":"Takeshi Kimura","orcid":"0000-0003-1179-8903","position":10,"is_corresponding":false},{"id":329488,"name":"Tomoyuki Nakamura","orcid":"0000-0002-8017-9818","position":11,"is_corresponding":false},{"id":329482,"name":"Masahito Horiguchi","orcid":"0000-0001-5325-3931","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase","abstract":"<jats:p>\n                    Great arteries, as well as lungs and skin, contain elastic fibers as important components to maintain their physiological functions. Although recent studies have revealed that a glycoprotein fibulin-4 (FBLN4) is indispensable for the assembly of mature elastic fibers, it remains to be elucidated how FBLN4 takes part in elastogenesis. Here, we report a dose-dependent requirement for FBLN4 in the development of the elastic fibers in arteries, and a specific role of FBLN4 in recruiting the elastin-cross-linking enzyme, lysyl oxidase (LOX). Reduced expression of\n                    <jats:italic>Fbln4</jats:italic>\n                    , which was achieved with a smooth muscle-specific Cre-mediated gene deletion, caused arterial stiffness. Electron-microscopic examination revealed disorganized thick elastic laminae with aberrant deposition of elastin. Aneurysmal dilation of the ascending aorta was found when the\n                    <jats:italic>Fbln4</jats:italic>\n                    expression level was reduced to an even lower level, whereas systemic\n                    <jats:italic>Fbln4</jats:italic>\n                    null mice died perinatally from rupture of the diaphragm. We also found a specific interaction between FBLN4 and the propeptide of LOX, which efficiently promotes assembly of LOX onto tropoelastin. These data suggest a mechanism of elastogenesis, in which a sufficient amount of FBLN4 is essential for tethering LOX to tropoelastin to facilitate cross-linking.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19855011","pmcid":"PMC2776456","openalex_id":"https://openalex.org/W19855011","authors":[],"funders":[],"total_grants":0,"fwci":1.1166,"citation_percentile":0.77588243,"influential_citations":0,"citation_trend":[{"year":2015,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2776456","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0908268106","host_type":"publisher"},{"url":"https://ir.canterbury.ac.nz/handle/10092/88","host_type":""},{"url":"http://hdl.handle.net/10092/88","host_type":"repository"}],"fields_of_study":["Geotechnical Engineering and Soil Stabilization","Geotechnical Engineering and Underground Structures","Geotechnical Engineering and Soil Mechanics","Animals","Arteries","Elastin","Extracellular Matrix Proteins","Gene Deletion","Immunohistochemistry","Mice","Mice, Knockout","Microscopy, Electron","Polymerase Chain Reaction","Protein Binding","Protein-Lysine 6-Oxidase"],"mesh_terms":["Arteries","Animals","Mice, Knockout","Mice","Elastin","Protein-Lysine 6-Oxidase","Extracellular Matrix Proteins","Microscopy, Electron","Immunohistochemistry","Polymerase Chain Reaction","Gene Deletion","Protein Binding"],"keywords":["Liquefaction","Lateral earth pressure","Group (periodic table)","Pile","Earth (classical element)","Stress (linguistics)","Geology","Geotechnical engineering","Mathematics","Chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Climate action"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T23:20:22.158904Z","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":[]}