1. Academic Validation
  2. Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Deficiency Attenuated Isoproterenol-Induced Cardiac Fibrosis via Reactive Oxygen Species/High Mobility Group Box 1 Protein Axis

Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Deficiency Attenuated Isoproterenol-Induced Cardiac Fibrosis via Reactive Oxygen Species/High Mobility Group Box 1 Protein Axis

  • Front Cell Dev Biol. 2020 Aug 11;8:713. doi: 10.3389/fcell.2020.00713.
Chen Liu 1 2 Tongtong Hu 1 2 Zhulan Cai 1 2 Qingwen Xie 1 2 Yuan Yuan 1 2 Ning Li 1 2 Saiyang Xie 1 2 Qi Yao 1 2 Jinhua Zhao 1 2 Qing Qing Wu 1 2 Qizhu Tang 1 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
Abstract

Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is involved in fibrosis of multiple organs, such as kidney, liver, lung, and the like. However, the role of NLRP3 in cardiac fibrosis is still controversial and remains unclear. The study aims to investigate the role of NLRP3 on cardiac fibrosis induced by isoproterenol (ISO). In vivo, NLRP3 knockout and wild-type mice were subcutaneously injected with ISO to induce the cardiac fibrosis model. The results showed that NLRP3 deficiency alleviated the cardiac fibrosis and inflammation induced by ISO. In vitro, neonatal rat ventricular myocytes (NRVMs) and primary adult mouse cardiac fibroblasts of NLRP3 knockout and wild-type mice were isolated and challenged with ISO. Adenovirus (Ad-) NLRP3 and small interfering RNAs targeting NLRP3 were used to transfect NRVMs to overexpress or knockdown NLRP3. We found that NLRP3 could regulate high-mobility group box 1 protein (HMGB1) secretion via Reactive Oxygen Species production in NRVMs and the HMGB1 secreted by NRVMs promoted the activation and proliferation of cardiac fibroblasts. Thus, we concluded that the NLRP3/Reactive Oxygen Species/HMGB1 pathway could be the underlying mechanism of ISO-induced cardiac fibrosis.

Keywords

cardiac fibrosis; heart failiure; high mobility group box 1 protein; nucleotide-binding oligomerization domain-like receptor 3; reactive oxygen species.

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