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Inhibition of Pendrin by a small molecule reduces Lipopolysaccharide-induced acute Lung Injury

Authors
 Eun Hye Lee  ;  Mi Hwa Shin  ;  Mia Gi  ;  Jinhong Park  ;  Doona Song  ;  Young-Min Hyun  ;  Ji-Hwan Ryu  ;  Je Kyung Seong  ;  Yoon Jeon  ;  Gyoonhee Han  ;  Wan Namkung  ;  Moo Suk Park  ;  Jae Young Choi 
Citation
 THERANOSTICS, Vol.10(22) : 9913-9922, 2020-08 
Journal Title
 THERANOSTICS 
Issue Date
2020-08
Keywords
ALI ; ARDS ; SLC26A4 ; inhibitor ; pendrin
Abstract
Rationale: Pendrin is encoded by SLC26A4 and its mutation leads to congenital hearing loss. Additionally, pendrin is up-regulated in inflammatory airway diseases such as chronic obstructive pulmonary disease, allergic rhinitis, and asthma. In this study, the effects of a novel pendrin inhibitor, YS-01, were investigated in an LPS-induced acute lung injury (ALI) mice model, and the mechanism underlying the effect of YS-01 was examined. Methods: Lipopolysaccharide (LPS, 10 mg/kg) was intranasally instilled in wild type (WT) and pendrin-null mice. YS-01 (10 mg/kg) was administered intra-peritoneally before or after LPS inhalation. Lung injury parameters were assessed in the lung tissue and bronchoalveolar lavage fluid (BALF). Pendrin levels in the BALF of 41 patients with acute respiratory distress syndrome (ARDS) due to pneumonia and 25 control (solitary pulmonary nodule) patients were also measured. Results: LPS instillation induced lung injury in WT mice but not in pendrin-null mice. Pendrin expression was increased by LPS stimulation both in vitro and in vivo. YS-01 treatment dramatically attenuated lung injury and reduced BALF cell counts and protein concentration after LPS instillation in WT mice. Proinflammatory cytokines and NF-κB activation were suppressed by YS-01 treatment in LPS-induced ALI mice. In BALF of patients whose ARDS was caused by pneumonia, pendrin expression was up-regulated compared to that in controls (mean, 24.86 vs. 6.83 ng/mL, P < 0.001). Conclusions: A novel pendrin inhibitor, YS-01, suppressed lung injury in LPS-induced ALI mice and our data provide a new strategy for the treatment of inflammatory airway diseases including sepsis-induced ALI.
Files in This Item:
T202004033.pdf Download
DOI
10.7150/thno.46417
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Ryu, Ji Hwan(유지환)
Lee, Eun Hye(이은혜) ORCID logo https://orcid.org/0000-0003-2570-3442
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
Hyun, Young-Min(현영민) ORCID logo https://orcid.org/0000-0002-0567-2039
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180107
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