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• W4295048416 abstract "Abstract Herein, we tested the hypothesis low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ion transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Intranasal instillation of LMW-HA (150μg/ml) to C57BL/6 mice inhibited their alveolar fluid clearance (AFC) by 75%, increased the epithelial lining fluid (ELF) thickness threefold, and lung wet/dry (W/D) ratio by 20% 24hrs later. Incubation of lung slices from mouse and human lungs with 150μg/ml LMW-HA decreased the open probability (P o ) of ENaC in ATII cell by more than 50% in 4hrs, inhibited amiloride sensitive short circuit current (SCC) 4hrs post exposure, and Cl − current through CFTR by more than 70%, and Na,K-ATPase current by 66% at 24hrs. In all cases the inhibitory effect of LMW-HA on lung epithelial ion transport in vivo, ex vivo, and in vitro preparations were reversed by the administration of 1μM of NPS2143, a CaSR inhibitor, or 150μg/ml HMW-HA. In HEK-293 cells co-transfected with CaSR and the calcium sensitive Cl − channel TMEM16-A, LMW-HA activated an inward Cl − current. These data are the first demonstration of the inhibitory effects of LMW-HA on lung epithelial ion and water transport, and are due to the activation of CaSR and its downstream signaling cascades." @default.
• W4295048416 created "2022-09-09" @default.
• W4295048416 creator A5001325524 @default.
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• W4295048416 date "2022-09-09" @default.
• W4295048416 modified "2023-09-26" @default.
• W4295048416 title "Low Molecular Weight Hyaluronan Inhibits Lung Epithelial Ion Channels by Activating the Calcium-Sensing Receptor" @default.
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• W4295048416 doi "https://doi.org/10.1101/2022.09.07.506946" @default.
• W4295048416 hasPublicationYear "2022" @default.
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