Quercetin ameliorates pulmonary fibrosis by inhibiting SphK1/S1P signaling

Biochem Cell Biol. 2018 Dec;96(6):742-751. doi: 10.1139/bcb-2017-0302. Epub 2018 Jun 25.

Abstract

Idiopathic pulmonary fibrosis is an agnogenic chronic disorder with high morbidity and low survival rate. Quercetin is a flavonoid found in a variety of herbs with anti-fibrosis function. In this study, bleomycin was employed to induce a pulmonary fibrosis mouse model. The quercetin administration ameliorated bleomycin-induced pulmonary fibrosis, evidenced by the expression level changes of hydroxyproline, fibronectin, α-smooth muscle actin, Collagen I, and Collagen III. Similar results were observed in transforming growth factor (TGF)-β-treated human embryonic lung fibroblast (HELF). The bleomycin or TGF-β administration caused the increase of sphingosine-1-phosphate (S1P) level in pulmonary tissue and HELF cells, as well as its activation-required kinase, sphingosine kinase 1 (SphK1), and its degradation enzyme, sphinogosine-1-phosphate lyase (S1PL). However, the increase of S1P, SphK1, and S1PL was attenuated by application of quercetin. In addition, the effect of quercetin on fibrosis was abolished by the ectopic expression of SphK1. The colocalization of SphK1/S1PL and fibroblast specific protein 1 (FSP1) suggested the roles of fibroblasts in pulmonary fibrosis. In summary, we demonstrated that quercetin ameliorated pulmonary fibrosis in vivo and in vitro by inhibiting SphK1/S1P signaling.

Keywords: bleomycin; bléomycine; fibrose pulmonaire; pulmonary fibrosis; quercetin; quercétine; sphingosine kinase 1; sphingosine-1-phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology
  • Lysophospholipids / antagonists & inhibitors*
  • Lysophospholipids / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Quercetin / pharmacology*
  • Signal Transduction / drug effects*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / antagonists & inhibitors
  • Sphingosine / metabolism

Substances

  • Lysophospholipids
  • sphingosine 1-phosphate
  • Quercetin
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Sphingosine