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• W2785223446 endingPage "L821" @default.
• W2785223446 startingPage "L808" @default.
• W2785223446 abstract "Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is no effective therapy. We hypothesized that HCl instilled intratracheally in C57BL/6 mice results in the formation of low-molecular weight hyaluronan (L-HA), which activates RhoA and Rho kinase (ROCK), causing airway hyperresponsiveness (AHR) and increased permeability. Furthermore, instillation of high-molecular weight hyaluronan (H-HA; Yabro) will reverse lung injury. We instilled HCl in C57BL/6 wild-type (WT), myeloperoxidase gene-deficient (MPO −/− ) mice, and CD44 gene-deficient (CD44 −/− ) mice. WT mice were also instilled intranasally with H-HA (Yabro) at 1 and 23 h post-HCl. All measurements were performed at 1, 5, or 24 h post-HCl. Instillation of HCl in WT but not in CD44 −/− resulted in increased inflammation, AHR, lung injury, and L-HA in the bronchoalveolar lavage fluid (BALF) 24 h post-HCl; L-HA levels and lung injury were significantly lower in HCl-instilled MPO −/− mice. Isolated perfused lungs of HCl instilled WT but not of CD44 −/− mice had elevated values of the filtration coefficient ( K f ). Addition of L-HA on the apical surface of human primary bronchial epithelial cell monolayer decreased barrier resistance ( R T ). H-HA significantly mitigated inflammation, AHR, and pulmonary vascular leakage at 24 h after HCl instillation and mitigated the increase of K f and R T, as well as ROCK2 phosphorylation. Increased H- and L-HA levels were found in the BALF of mechanically ventilated patients but not in healthy volunteers. HCl instillation-induced lung injury is mediated by the L-HA-CD44-RhoA-ROCK2 signaling pathway, and H-HA is a potential novel therapeutic agent for acid aspiration-induced lung injury." @default.
• W2785223446 created "2018-02-02" @default.
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• W2785223446 date "2018-05-01" @default.
• W2785223446 modified "2023-10-17" @default.
• W2785223446 title "Instillation of hyaluronan reverses acid instillation injury to the mammalian blood gas barrier" @default.
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• W2785223446 doi "https://doi.org/10.1152/ajplung.00510.2017" @default.
• W2785223446 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6008127" @default.
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• W2785223446 hasPublicationYear "2018" @default.
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