tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol
. 2023 Jul 21.
doi: 10.1165/rcmb.2022-0351OC. Online ahead of print. RAGE Is a Receptor for SARS-CoV-2 N Protein and Mediates N Protein-induced Acute Lung Injury
Jie Xia[SUP] 1 [/SUP], Jiangmei Wang[SUP] 1 [/SUP], Liyang Ying[SUP] 1 [/SUP], Ruoqiong Huang[SUP] 1 [/SUP], Kai Zhang[SUP] 2 [/SUP], Ruoyang Zhang[SUP] 1 [/SUP], Wenqi Tang[SUP] 1 [/SUP], Qi Xu[SUP] 3 [/SUP], Dengming Lai[SUP] 4 5 [/SUP], Yan Zhang[SUP] 6 [/SUP], Yaoqin Hu[SUP] 1 [/SUP], Xiaodie Zhang[SUP] 1 [/SUP], Ruoxi Zang[SUP] 1 [/SUP], Jiajie Fan[SUP] 1 [/SUP], Qiang Shu[SUP] 1 [/SUP], Jianguo Xu[SUP] 7 [/SUP]
Affiliations
SARS-CoV-2 nucleocapsid protein (N-protein) rises early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in lung inflammatory response remains poorly understood. The goal of this study was to determine whether receptor for advanced glycation endproducts (RAGE) participated in N-protein-induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein-protein interaction. To determine the signaling mechanism in vitro, cells were treated with recombinant N-protein and assayed for the activation of RAGE/mitogen-activated protein kinase/NF-ĸB pathway. RAGE deficiency mice and antagonist were applied to study N-protein-induced acute lung injury in vivo. Binding between N-protein and RAGE was confirmed via flow cytometry-based binding assay, surface plasmon resonance, and enzyme-linked immunosorbent assay. Pull-down and co-immunoprecipitation assays revealed that N-protein bound RAGE via both N-terminal and C-terminal domains. In vitro, N-protein activated RAGE-ERK1/2-NF-ĸB signaling pathway and induced proinflammatory response. RAGE deficiency subdued N-protein-induced proinflammatory signaling and response. In vivo, RAGE was upregulated in the bronchioalveolar lavage and lung tissue after recombinant N-protein insult. RAGE deficiency and small molecule antagonist partially protected mice from N-protein-induced acute lung injury. Our study demonstrated that RAGE is a receptor for N-protein. RAGE is partially responsible for N-protein-induced acute lung injury and has the potential to become a therapeutic target for treating Coronavirus disease 2019. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: SARS-CoV-2 , receptor for advanced glycation endproducts , nucleocapsid protein , receptor , acute lung injury.
. 2023 Jul 21.
doi: 10.1165/rcmb.2022-0351OC. Online ahead of print. RAGE Is a Receptor for SARS-CoV-2 N Protein and Mediates N Protein-induced Acute Lung Injury
Jie Xia[SUP] 1 [/SUP], Jiangmei Wang[SUP] 1 [/SUP], Liyang Ying[SUP] 1 [/SUP], Ruoqiong Huang[SUP] 1 [/SUP], Kai Zhang[SUP] 2 [/SUP], Ruoyang Zhang[SUP] 1 [/SUP], Wenqi Tang[SUP] 1 [/SUP], Qi Xu[SUP] 3 [/SUP], Dengming Lai[SUP] 4 5 [/SUP], Yan Zhang[SUP] 6 [/SUP], Yaoqin Hu[SUP] 1 [/SUP], Xiaodie Zhang[SUP] 1 [/SUP], Ruoxi Zang[SUP] 1 [/SUP], Jiajie Fan[SUP] 1 [/SUP], Qiang Shu[SUP] 1 [/SUP], Jianguo Xu[SUP] 7 [/SUP]
Affiliations
- PMID: 37478333
- DOI: 10.1165/rcmb.2022-0351OC
SARS-CoV-2 nucleocapsid protein (N-protein) rises early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in lung inflammatory response remains poorly understood. The goal of this study was to determine whether receptor for advanced glycation endproducts (RAGE) participated in N-protein-induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein-protein interaction. To determine the signaling mechanism in vitro, cells were treated with recombinant N-protein and assayed for the activation of RAGE/mitogen-activated protein kinase/NF-ĸB pathway. RAGE deficiency mice and antagonist were applied to study N-protein-induced acute lung injury in vivo. Binding between N-protein and RAGE was confirmed via flow cytometry-based binding assay, surface plasmon resonance, and enzyme-linked immunosorbent assay. Pull-down and co-immunoprecipitation assays revealed that N-protein bound RAGE via both N-terminal and C-terminal domains. In vitro, N-protein activated RAGE-ERK1/2-NF-ĸB signaling pathway and induced proinflammatory response. RAGE deficiency subdued N-protein-induced proinflammatory signaling and response. In vivo, RAGE was upregulated in the bronchioalveolar lavage and lung tissue after recombinant N-protein insult. RAGE deficiency and small molecule antagonist partially protected mice from N-protein-induced acute lung injury. Our study demonstrated that RAGE is a receptor for N-protein. RAGE is partially responsible for N-protein-induced acute lung injury and has the potential to become a therapeutic target for treating Coronavirus disease 2019. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: SARS-CoV-2 , receptor for advanced glycation endproducts , nucleocapsid protein , receptor , acute lung injury.