{"doi":"10.1016/j.matbio.2023.02.002","title":"Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor","abstract":"Herein, we tested the hypothesis that low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ions transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Twenty-four hours post intranasal instillation of 50–150 µg/ml LMW-HA to C57BL/6 mice, there was a 75% inhibition of alveolar fluid clearance (AFC), a threefold increase in the epithelial lining fluid (ELF) depth, and a 20% increase in lung wet/dry (W/D) ratio. Incubation of human and mouse precision cut lung slices with 150 µg/ml LMW-HA reduced the activity and the open probability (Po) of epithelial sodium channel (ENaC) in alveolar epithelial type 2 (ATII) cells, and in mouse tracheal epithelial cells (MTEC) monolayers as early as 4 h. The Cl− current through cystic fibrosis transmembrane conductance regulator (CFTR) and the activity of Na,K-ATPase were both inhibited by more than 66% at 24 h. The inhibitory effects of LMW-HA on ion channels were reversed by 1 µM NPS-2143, or 150 µg/ml high molecular weight hyaluronan (HMW-HA). In HEK-293 cells expressing the calcium-sensitive Cl− channel TMEM16-A, CaSR was required for the activation of the Cl− current by LMW-HA. This is the first demonstration of lung ions and water transport inhibition by LMW-HA, and its mediation through the activation of CaSR.","journal":"Matrix Biology","year":2023,"id":345638,"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":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":441409,"name":"Weifeng Song","orcid":"0000-0001-5716-1698","position":1,"is_corresponding":false},{"id":236993,"name":"Zhihong Yu","orcid":"0000-0001-8304-1833","position":2,"is_corresponding":false},{"id":609805,"name":"Shaoyan Zhang","orcid":"0000-0001-8412-6150","position":3,"is_corresponding":false},{"id":72298,"name":"Anoma Nellore","orcid":"0000-0002-2489-2838","position":4,"is_corresponding":false},{"id":968312,"name":"Charles W. Hoopes","orcid":"0000-0001-7658-555X","position":5,"is_corresponding":false},{"id":416507,"name":"Bradford A. Woodworth","orcid":"0000-0003-3292-9167","position":6,"is_corresponding":false},{"id":382562,"name":"Sadis Matalon","orcid":"0000-0003-0683-3700","position":7,"is_corresponding":false},{"id":404775,"name":"Ahmed Lazrak","orcid":"0000-0002-4127-1937","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-19T01:11:44.152490Z","pmid":"36758905","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":[]}