{"doi":"10.1172/jci136164","title":"Decreased lymphatic HIF-2α accentuates lymphatic remodeling in lymphedema","abstract":"Pathologic lymphatic remodeling in lymphedema evolves during periods of tissue inflammation and hypoxia through poorly defined processes. In human and mouse lymphedema, there is a significant increase of hypoxia inducible factor 1 α (HIF-1α), but a reduction of HIF-2α protein expression in lymphatic endothelial cells (LECs). We questioned whether dysregulated expression of these transcription factors contributes to disease pathogenesis and found that LEC-specific deletion of Hif2α exacerbated lymphedema pathology. Even without lymphatic vascular injury, the loss of LEC-specific Hif2α caused anatomic pathology and a functional decline in fetal and adult mice. These findings suggest that HIF-2α is an important mediator of lymphatic health. HIF-2α promoted protective phosphorylated TIE2 (p-TIE2) signaling in LECs, a process also replicated by upregulating TIE2 signaling through adenovirus-mediated angiopoietin-1 (Angpt1) gene therapy. Our study suggests that HIF-2α normally promotes healthy lymphatic homeostasis and raises the exciting possibility that restoring HIF-2α pathways in lymphedema could mitigate long-term pathology and disability.","journal":"Journal of Clinical Investigation","year":2020,"id":100824,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"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":292030,"name":"Wen Tian","orcid":"0000-0002-0569-318X","position":1,"is_corresponding":false},{"id":494957,"name":"Eric J. Granucci","orcid":null,"position":2,"is_corresponding":false},{"id":494254,"name":"Allen B. Tu","orcid":"0000-0003-2978-995X","position":3,"is_corresponding":false},{"id":292032,"name":"Dong-Eon Kim","orcid":"0000-0002-1674-1263","position":4,"is_corresponding":false},{"id":356955,"name":"Petra Dahms","orcid":"0000-0001-7989-8797","position":5,"is_corresponding":false},{"id":494255,"name":"Shravani Pasupneti","orcid":"0000-0002-7112-601X","position":6,"is_corresponding":false},{"id":494256,"name":"Gongyong Peng","orcid":"0000-0002-3187-3387","position":7,"is_corresponding":false},{"id":494257,"name":"Yesl Kim","orcid":"0000-0001-7749-641X","position":8,"is_corresponding":false},{"id":494958,"name":"Amber H. Lim","orcid":null,"position":9,"is_corresponding":false},{"id":494258,"name":"F. Hernán Espinoza","orcid":"0000-0002-1855-1914","position":10,"is_corresponding":false},{"id":494259,"name":"Matthew T. Cribb","orcid":"0000-0001-7691-3998","position":11,"is_corresponding":false},{"id":361674,"name":"J. Brandon Dixon","orcid":"0000-0003-0351-4587","position":12,"is_corresponding":false},{"id":292034,"name":"Stanley G. Rockson","orcid":"0000-0003-1253-474X","position":13,"is_corresponding":false},{"id":334390,"name":"Gregg L. Semenza","orcid":"0000-0002-0913-211X","position":14,"is_corresponding":false},{"id":292033,"name":"Mark R. Nicolls","orcid":"0000-0001-9473-7422","position":15,"is_corresponding":false},{"id":292031,"name":"Xinguo Jiang","orcid":"0000-0003-3266-9238","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T22:39:01.863288Z","pmid":"32673288","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":[]}