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Retraction: Endothelial cell‐specific deficiency of the adenosine deaminase ADAR1 aggravates LPS‐induced lung injury in mice via an MDA5‐independent pathway
Author(s) -
Xiaolin Wang,
Rong Yan,
Zhen Zhang,
Guang-Zhi Cong,
Zhongjie Yi,
Yiping Leng,
Alex F. Chen
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13754
Subject(s) - adenosine deaminase , adenosine deaminase deficiency , lung , medicine , chemistry , adenosine , endocrinology
Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to participate in the regulation of endothelial cells (ECs), as well as local and systemic inflammatory responses. Here, we find that bacterial lipopolysaccharide (LPS)-induced upregulation of ADAR1 in lung ECs is impaired in aged mice, an animal model with high rates of sepsis and mortality. Endothelial cell-specific ADAR1 knockout (ADAR1 ECKO ) mice suffer from higher mortality rates, aggravated lung injury, and increased vascular permeability under LPS challenge. In primary ADAR1 knockout ECs, expression of the melanoma differentiation-associated gene 5 (MDA5), a downstream effector of ADAR1, is significantly elevated. MDA5 knockout completely rescues the postnatal offspring death of ADAR1 ECKO mice. However, there is no reduction in mortality or apoptosis in lung cells of ADAR1 ECKO /MDA5 -/- mice challenged with LPS, indicating the involvement of an MDA5-independent mechanism in this process.