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

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

  • Int Immunopharmacol. 2022 Aug;109:108805. doi: 10.1016/j.intimp.2022.108805.
Renzi Zhang 1 Yiwen Tan 2 Chaoying Yong 1 Yang Jiao 1 Xumao Tang 3 Daoxin Wang 4
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: drtangxm@qq.com.
  • 4 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: wangdaoxin0163@163.com.
Abstract

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 LPS-induced 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 LPS-induced 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 α-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.

Keywords

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

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