期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.641973
关键词
HMGB1; TGF-β 1; cardiac allograft vasculopathy; transplantation; fibrosis
类别
资金
- National Natural Sciences Foundation of China [81072466, 81901586]
- China Postdoctoral Science Foundation [2015M572148]
The study revealed that HMGB1 contributes to the progression of CAV/fibrosis by promoting the activation of the TGF-β1/Smad signaling pathway, and neutralizing HMGB1 can prolong allograft survival and attenuate fibrosis. Targeting HMGB1 may be a potential therapeutic strategy for inhibiting cardiac allograft fibrosis and dysfunction.
Cardiac allograft vasculopathy (CAV) charactered with aberrant remodeling and fibrosis usually leads to the loss of graft after heart transplantation. Our previous work has reported that extracellular high-mobility group box 1 (HMGB1) participated in the CAV progression via promoting inflammatory cells infiltration and immune damage. The aim of this study was to investigate the involvement of HMGB1 in the pathogenesis of CAV/fibrosis and potential mechanisms using a chronic cardiac rejection model in mice. We found high levels of transforming growth factor (TGF)-beta 1 in cardiac allografts after transplantation. Treatment with HMGB1 neutralizing antibody markedly prolonged the allograft survival accompanied by attenuated fibrosis of cardiac allograft, decreased fibroblasts-to-myofibroblasts conversion, and reduced synthesis and release of TGF-beta 1. In addition, recombinant HMGB1 stimulation promoted release of active TGF-beta 1 from cardiac fibroblasts and macrophages in vitro, and subsequent phosphorylation of Smad2 and Smad3 which were downstream of TGF-beta 1 signaling. These data indicate that HMGB1 contributes to the CAV/fibrosis via promoting the activation of TGF-beta 1/Smad signaling. Targeting HMGB1 might become a new therapeutic strategy for inhibiting cardiac allograft fibrosis and dysfunction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据