{"doi":"10.3389/fcell.2025.1659266","title":"Editorial: Lymphatic system: organ specific functions in health and disease, volume II","abstract":"The lymphatic system plays central roles in the maintenance of fluid balance, clearance of macromolecules, fat absorption, and immune surveillance. Lymphatic functions vary notably across organs and physiological contexts and play important roles in numerous pathological conditions (Janardhan et al., 2023, Mehrara et al., 2023). Despite recent progress in understanding these functions, the cellular and molecular mechanisms that govern the formation and regulation of lymphatic vascular heterogeneity in various organs and tissues remain incompletely defined. This Research Topic brought together a collection of three original research articles and five review articles from diverse disciplines -developmental biology, lymphatic malformations, inflammation, pathophysiology, bioengineering, and potential treatments -to deepen our understanding of organ-specific lymphatic functions in health and disease.Vascular endothelial growth factor receptor 3 (VEGFR3) signaling in lymphatic endothelial cells (Kuonqui et al., 2025). This is a comprehensive review detailing VEGFR3 pathway regulation in lymphatic development and function. It outlines key mediators downstream of the VEGFC/VEGFR3 signaling pathway in lymphatic endothelial cells (LECs) and their functional roles in lymphatic vessel physiology and discusses the regulation of overall VEGFR3 activity in lymphatic vessels.Lymphangiocrine signaling pathways in the heart and intestine (Kurup et al., 2023).Recent evidence indicates that LECs secrete paracrine (lymphoangiocrine) molecules that are specific to organ tissues. This review article provides a comprehensive overview of the crosstalk between LECs and adjacent cells to augment tissue regeneration in cardiac and intestinal disease. The roles of lymphangiocrine factors, including Reelin, Apelin, Adenomedulin, and R-Spondin 3, in the heart and intestine in tissue maintenance and self-renewal following injury are discussed. (Davis et al., 2024). This original research article is aimed at investigating the developmental progression of functional lymphatic valve leaflets that prevent backflow to maintain a unidirectional flow.Lymphatic valve development includes four main stages (stages 1-4) of morphogenic dynamics. Ex vivo tests of valve function using isolated murine mesenteric collecting lymphatic vessels reveal that valves become functional, preventing backflow between stages 3 and 4 of development. (Fernandes et al., 2023). Somatic activating mutations in KRAS cause complex lymphatic anomalies (CLAs). However, its pathogenesis remains largely unknown. This original research article demonstrates that hyperactive KRAS signaling caused by the KRAS mutation (p.G12D) results in enlarged lymphatic vessels in mouse embryos. This mutation induces cell spindling, proliferation, and migration in vitro. Importantly, this study also reveals the therapeutic potential of targeting hyperactive KRAS signaling in lymphatic anomalies associated with somatic KRAS mutations.These articles provide insights into the various functions of lymphatic vessels in different organs and tissues and how the extracellular signaling pathways, ranging from VEGFC/VEGFR3 to lymphangiocrine factors, contribute to maintaining proper lymphatic function and tissue homeostasis.Secondary lymphedema molecular pathology (Lee and Kim, 2024). This review article provides a comprehensive overview of the pathophysiology of secondary lymphedema, a condition that arises due to injury or obstruction of the lymphatic system, and most commonly and globally, filariasis. It highlights three consequences in lymphedema: (1) chronic inflammation-mediated lymphangiogenesis, which is dependent on the VEGF-C/VEGFR axis, (2) adipocyte hypertrophy and adipose tissue deposition, and (3) tissue fibrosis. Despite surgical treatments of reconstructing the lymphatic system to facilitate lymphatic fluid drainage, there is a limitation of their effectiveness in treating already damaged lymphatic vessels.","journal":"Frontiers in Cell and Developmental Biology","year":2025,"id":571643,"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":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331868,"name":"Young‐Kwon Hong","orcid":"0000-0001-8245-875X","position":1,"is_corresponding":false},{"id":312371,"name":"Tsutomu Kume","orcid":"0000-0002-6005-5316","position":2,"is_corresponding":false},{"id":245968,"name":"Zoltán Jakus","orcid":"0000-0002-6304-2369","position":0,"is_corresponding":true}],"reference_count":2,"raw_metadata":null,"created_at":"2026-07-19T02:57:19.669553Z","pmid":"40800682","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":[]}