The inhibition effect and mechanism of SY0916 on pulmonary fibrosis.
SY0916 is a new platelet-activating factor receptor antagonist developed by our institute. In this study, the inhibitory effect of SY0916 on pulmonary fibrosis was investigated in epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) in vitro and a pulmonary fibrosis animal model induced by bleomycin (BLM). The results showed that SY0916 could inhibit the EMT of A549 cells induced with TGF-β1. In vivo, SY0916 administration significantly ameliorated the BLM-mediated histological changes, reduced main biochemical parameters related to pulmonary fibrosis such as hydroxyproline and glutathione, and also notably attenuated the expression of key pro-fibrotic mediator, TGF-β1. These findings demonstrated that SY0916 could possibly be developed as a promising candidate for the treatment of pulmonary fibrosis.
a Department of Pharmacology , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
Hai-Jing
HJ
Zhang
Wen-Yang
WY
Han
Shan-Ying
SY
Peng
Yang
Y
Liu
Lian-Qiu
LQ
Wu
Wen-Jie
WJ
Wang
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007659:Ketones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D007659:Ketones; D010880:Piperidines; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C550310:SY0916; D053773:Transforming Growth Factor beta1; C039351:platelet activating factor receptor; D001761:Bleomycin
epithelial–mesenchymal transition; platelet-activating factor receptor antagonist; pulmonary fibrosis