Long Shuang Huang1, Evgeny V Berdyshev2, John T Tran3, Lishi Xie4, Jiwang Chen2, David L Ebenezer5, Biji Mathew2, Irina Gorshkova2, Wei Zhang6, Sekhar P Reddy7, Anantha Harijith7, Gang Wang8, Carol Feghali-Bostwick9, Imre Noth10, Shwu-Fan Ma10, Tong Zhou11, Wenli Ma11, Joe G N Garcia11, Viswanathan Natarajan12. 1. Department of Pharmacology, The University of Illinois, Chicago, Illinois, USA. 2. Department of Medicine,The University of Illinois, Chicago, Illinois, USA. 3. Department of Biology, The University of Illinois, Chicago, Illinois, USA. 4. Department of Urology, The University of Illinois, Chicago, Illinois, USA. 5. Department of Biochemistry and Molecular Genetics, The University of Illinois, Chicago, Illinois, USA. 6. Department of Pharmacology, The University of Illinois, Chicago, Illinois, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 7. Department of Pediatrics, The University of Illinois, Chicago, Illinois, USA. 8. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China. 9. Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, South Carolina, USA. 10. Department of Medicine, University of Chicago, Chicago, Illinois, USA. 11. Department of Medicine, University of Arizona, Tucson, Arizona, USA. 12. Department of Pharmacology, The University of Illinois, Chicago, Illinois, USA Department of Medicine,The University of Illinois, Chicago, Illinois, USA.
Abstract
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. Sphingosine-1-phosphate (S1P) signalling plays a critical role in pulmonary fibrosis. METHODS: S1P lyase (S1PL) expression in peripheral blood mononuclear cells (PBMCs) was correlated with pulmonary functions and overall survival; used a murine model to check the role of S1PL on the fibrogenesis and a cell culture system to study the effect of S1PL expression on transforming growth factor (TGF)-β- and S1P-induced fibroblast differentiation. RESULTS: S1PL expression was upregulated in fibrotic lung tissues and primary lung fibroblasts isolated from patients with IPF and bleomycin-challenged mice. TGF-β increased the expression of S1PL in human lung fibroblasts via activation and binding of Smad3 transcription factor to Sgpl1 promoter. Overexpression of S1PL attenuated TGF-β-induced and S1P-induced differentiation of human lung fibroblasts through regulation of the expression of LC3 and beclin 1. Knockdown of S1PL (Sgpl1(+/-)) in mice augmented bleomycin-induced pulmonary fibrosis, and patients with IPF reduced Sgpl1 mRNA expression in PBMCs exhibited higher severity of fibrosis and lower survival rate. CONCLUSION: These studies suggest that S1PL is a novel endogenous suppressor of pulmonary fibrosis in human IPF and animal models. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. Sphingosine-1-phosphate (S1P) signalling plays a critical role in pulmonary fibrosis. METHODS:S1P lyase (S1PL) expression in peripheral blood mononuclear cells (PBMCs) was correlated with pulmonary functions and overall survival; used a murine model to check the role of S1PL on the fibrogenesis and a cell culture system to study the effect of S1PL expression on transforming growth factor (TGF)-β- and S1P-induced fibroblast differentiation. RESULTS:S1PL expression was upregulated in fibrotic lung tissues and primary lung fibroblasts isolated from patients with IPF and bleomycin-challenged mice. TGF-β increased the expression of S1PL in human lung fibroblasts via activation and binding of Smad3 transcription factor to Sgpl1 promoter. Overexpression of S1PL attenuated TGF-β-induced and S1P-induced differentiation of human lung fibroblasts through regulation of the expression of LC3 and beclin 1. Knockdown of S1PL (Sgpl1(+/-)) in mice augmented bleomycin-induced pulmonary fibrosis, and patients with IPF reduced Sgpl1 mRNA expression in PBMCs exhibited higher severity of fibrosis and lower survival rate. CONCLUSION: These studies suggest that S1PL is a novel endogenous suppressor of pulmonary fibrosis in human IPF and animal models. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Yong Huang; Shwu-Fan Ma; Milena S Espindola; Rekha Vij; Justin M Oldham; Gary B Huffnagle; John R Erb-Downward; Kevin R Flaherty; Beth B Moore; Eric S White; Tong Zhou; Jianrong Li; Yves A Lussier; MeiLan K Han; Naftali Kaminski; Joe G N Garcia; Cory M Hogaboam; Fernando J Martinez; Imre Noth Journal: Am J Respir Crit Care Med Date: 2017-07-15 Impact factor: 21.405
Authors: Cody A Schott; Christian Ascoli; Yue Huang; David L Perkins; Patricia W Finn Journal: Am J Respir Crit Care Med Date: 2020-03-01 Impact factor: 21.405