{"doi":"10.1101/2020.03.24.006270","title":"Fibrinolytic niche is requested for alveolar type 2 cell-mediated alveologenesis and injury repair","abstract":"ABSTRACT COVID-19, SARS, and MERS are featured by fibrinolytic dysfunction. To test the role of the fibrinolytic niche in the regeneration of alveolar epithelium, we compared the self-renewing capacity of alveolar epithelial type 2 (AT2) cells and its differentiation to AT1 cells between wild type (wt) and fibrinolytic niche deficient mice ( Plau −/− and Serpine1 Tg ). A significant reduction in both proliferation and differentiation of deficient AT2 cells was observed in vivo and in 3D organoid cultures. This decrease was mainly restored by uPA derived A6 peptide, a binding fragment to CD44 receptors. The proliferative and differential rate of CD44 + AT2 cells was greater than that of CD44 − controls. There was a reduction in transepithelial ion transport in deficient monolayers compared to wt cells. Moreover, we found a marked suppression in total AT2 cells and CD44 + subpopulation in lungs from brain dead patients with acute respiratory distress syndrome (ARDS) and a mouse model infected by influenza viruses. Thus, we demonstrate that the fibrinolytic niche can regulate AT2-mediated homeostasis and regeneration via a novel uPA-A6-CD44 + -ENaC cascade.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123553,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":505932,"name":"Runzhen Zhao","orcid":"0000-0003-4537-6020","position":1,"is_corresponding":false},{"id":566456,"name":"Mo Zhang","orcid":"0000-0003-3231-5915","position":2,"is_corresponding":false},{"id":566457,"name":"Krishan Gopal Jain","orcid":"0000-0002-1392-7038","position":3,"is_corresponding":false},{"id":317757,"name":"Jianjun Chang","orcid":"0000-0001-6707-1944","position":4,"is_corresponding":false},{"id":566458,"name":"Satoshi Komatsu","orcid":"0000-0002-9180-9053","position":5,"is_corresponding":false},{"id":339016,"name":"Xiaohui Fang","orcid":"0000-0003-2731-5021","position":6,"is_corresponding":false},{"id":356249,"name":"Beiyun Zhou","orcid":"0000-0002-9084-5933","position":7,"is_corresponding":false},{"id":328693,"name":"Jiurong Liang","orcid":"0000-0001-5179-5016","position":8,"is_corresponding":false},{"id":328696,"name":"Dianhua Jiang","orcid":"0000-0002-4508-3829","position":9,"is_corresponding":false},{"id":566842,"name":"Mistuo Ikebe","orcid":null,"position":10,"is_corresponding":false},{"id":231443,"name":"Michael A. Matthay","orcid":"0000-0003-3039-8155","position":11,"is_corresponding":false},{"id":505938,"name":"Hong‐Long Ji","orcid":"0000-0002-3228-7144","position":12,"is_corresponding":false},{"id":505933,"name":"Gibran Ali","orcid":"0000-0002-2997-3514","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","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":[]}