{"doi":"10.1152/ajplung.00158.2021","title":"Lysyl oxidase regulation and protein aldehydes in the injured newborn lung","abstract":"During newborn lung injury, excessive activity of lysyl oxidases (LOXs) disrupts extracellular matrix (ECM) formation. Previous studies indicate that TGFβ activation in the O 2 -injured mouse pup lung increases lysyl oxidase (LOX) expression. But how TGFβ regulates this, and whether the LOXs generate excess pulmonary aldehydes are unknown. First, we determined that O 2 -mediated lung injury increases LOX protein expression in TGFβ-stimulated pup lung interstitial fibroblasts. This regulation appeared to be direct; this is because TGFβ treatment also increased LOX protein expression in isolated pup lung fibroblasts. Then using a fibroblast cell line, we determined that TGFβ stimulates LOX expression at a transcriptional level via Smad2/3-dependent signaling. LOX is translated as a pro-protein that requires secretion and extracellular cleavage before assuming amine oxidase activity and, in some cells, reuptake with nuclear localization. We found that pro-LOX is processed in the newborn mouse pup lung. Also, O 2 -mediated injury was determined to increase pro-LOX secretion and nuclear LOX immunoreactivity particularly in areas populated with interstitial fibroblasts and exhibiting malformed ECM. Then, using molecular probes, we detected increased aldehyde levels in vivo in O 2 -injured pup lungs, which mapped to areas of increased pro-LOX secretion in lung sections. Increased activity of LOXs plays a critical role in the aldehyde generation; an inhibitor of LOXs prevented the elevation of aldehydes in the O 2 -injured pup lung. These results reveal new mechanisms of TGFβ and LOX in newborn lung disease and suggest that aldehyde-reactive probes might have utility in sensing the activation of LOXs in vivo during lung injury.","journal":"American Journal of Physiology-Lung Cellular and Molecular Physiology","year":2021,"id":184268,"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":12,"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":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":738871,"name":"Rose C. Mahoney","orcid":"0000-0002-8137-0091","position":1,"is_corresponding":false},{"id":738872,"name":"Zehedina Khatun","orcid":"0000-0002-0116-3042","position":2,"is_corresponding":false},{"id":392222,"name":"Howard H. Chen","orcid":"0000-0002-5145-0584","position":3,"is_corresponding":false},{"id":479661,"name":"Christopher Nguyen","orcid":"0000-0003-1475-2329","position":4,"is_corresponding":false},{"id":334441,"name":"Peter Caravan","orcid":"0000-0002-3179-6537","position":5,"is_corresponding":false},{"id":737290,"name":"Jesse D. Roberts","orcid":"0000-0003-0271-275X","position":6,"is_corresponding":false},{"id":739415,"name":"Ying Zhong","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T23:48:26.340498Z","pmid":"34878944","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":[]}