Pirfenidone ameliorates early pulmonary fibrosis in LPS-induced acute respiratory distress syndrome by inhibiting endothelial-to-mesenchymal transition via the Hedgehog signaling pathway

作者全名："Zhang, Renzi; Tan, Yiwen; Yong, Chaoying; Jiao, Yang; Tang, Xumao; Wang, Daoxin"

作者地址："[Zhang, Renzi; Yong, Chaoying; Jiao, Yang; Tang, Xumao; Wang, Daoxin] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, Chongqing, Peoples R China; [Tan, Yiwen] Chongqing Med Univ, Dept Pathol, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Tang, XM; Wang, DX (通讯作者)，Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000804675800003

JCR分区：Q1

影响因子：5.6

年份：2022

卷号：109

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Acute respiratory distress syndrome; Acute lung injury; Pirfenidone; Inflammation; Fibrosis; Endothelial-to-mesenchymal transition; Hedgehog

摘要："Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases. However, the role of PFD in the course of EndMT in LPSinduced ARDS remains poorly understood. The purpose of this study was to explore the anti-EndMT effects of PFD on pulmonary fibrosis after LPS-induced ARDS. First, we determined that PFD significantly reduced LPSinduced ARDS, as shown by significant pathological alterations, and alleviated the oxidative stress and inflammatory response in vitro and in vivo. Furthermore, PFD decreased pulmonary fibrosis in LPS-induced ARDS by inhibiting EndMT and reduced the expression levels of Hedgehog (HH) pathway target genes, such as Gli1 and alpha-SMA, after LPS induction. In summary, this study confirmed that inhibiting the HH pathway by PFD could decrease pulmonary fibrosis by downregulating EndMT in LPS-induced ARDS. In conclusion, we demonstrate that PFD is a promising agent to attenuate pulmonary fibrosis following ARDS in the future."

基金机构："National Natural Science Founda-tion of China [81670071]; Natural Science Foundation of Chongqing, China [cstc2019jcyj-zdxmX0031]"

基金资助正文："Funding This study was supported by the National Natural Science Founda-tion of China (Grant no. 81670071) , and the Natural Science Foundation of Chongqing, China (Grant no. cstc2019jcyj-zdxmX0031) ."