肺纤维化
癌症研究
上皮-间质转换
肺
信号转导
纤维化
SMAD公司
炎症体
下调和上调
化学
Wnt信号通路
波形蛋白
医学
病理
炎症
免疫学
内科学
免疫组织化学
生物化学
基因
作者
Sang Yeon Kim,Sunjoo Park,Ri Cui,Eun Bong Lee,Hojung Choi,Mohamed El-Agamy Farh,Hannah Jo,Jae Hee Lee,Hyo Jeong Song,Yoonjin Lee,Yun Sil Lee,Bong Yong Lee,Jaeho Cho
标识
DOI:10.3390/ijms242216265
摘要
Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1β and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.
科研通智能强力驱动
Strongly Powered by AbleSci AI