Contribution of Connexin Hemichannels to the Pathogenesis of Acute Lung Injury
Joint Authors
Zhang, Yijie
Wang, Shuaiwei
Zhou, Nannan
Chen, Na
Sun, Yafang
Miller, Edmund J.
Li, Wei
Bai, Yu
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-11-18
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Connexin (Cx) family members form hemichannels (HCs) and gap junctions (GJs).
Biological functions of Cx HCs have not been adequately characterized due to the inability to selectively target HCs or GJs.
Recently, we developed a 6-mer peptide mimetic (P5) of the first extracellular loop of Cx43 and showed that it can block the permeability of HCs but not GJs formed by Cx43.
In this study, we further characterized the HC blocking property of P5 and investigated the role of Cx HCs in acute lung injury (ALI).
We found that P5 administration decreased HC permeability, in pulmonary microvascular endothelial cells, HepG2 cells, and even Cx43-deficient astrocytes, which express different sets of Cxs, suggesting that P5 is a broad spectrum Cx HC blocker.
In addition, P5 reduced HC permeability of alveolar cells in vivo.
Moreover, P5 decreased endotoxin-induced release, by vascular endothelial cells in vitro, of high mobility group box protein 1 (HMGB1), a critical mediator of acute lung injury (ALI), and reduced HMGB1 accumulation in bronchoalveolar lavage fluid (BALF) of mice subjected to intratracheal endotoxin instillation.
Furthermore, P5 administration resulted in a significant decrease in the concentrations of ALT, AST, and LDH in the BALF, the accumulation of leukocytes in alveoli, and the mortality rate of mice subjected to ALI.
Wright-Giemsa staining showed that P5 caused similar reductions of both neutrophils and monocytes in BALF of ALI mice.
Together, these results suggest that Cx HCs mediate HMGB1 release, augment leukocyte recruitment, and contribute to ALI pathology.
American Psychological Association (APA)
Wang, Shuaiwei& Sun, Yafang& Bai, Yu& Zhou, Nannan& Chen, Na& Miller, Edmund J.…[et al.]. 2020. Contribution of Connexin Hemichannels to the Pathogenesis of Acute Lung Injury. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1192024
Modern Language Association (MLA)
Wang, Shuaiwei…[et al.]. Contribution of Connexin Hemichannels to the Pathogenesis of Acute Lung Injury. Mediators of Inflammation No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1192024
American Medical Association (AMA)
Wang, Shuaiwei& Sun, Yafang& Bai, Yu& Zhou, Nannan& Chen, Na& Miller, Edmund J.…[et al.]. Contribution of Connexin Hemichannels to the Pathogenesis of Acute Lung Injury. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1192024
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192024