• Long Shuang Huang, Evgeny V Berdyshev, John T Tran, Lishi Xie, Jiwang Chen, David L Ebenezer, Biji Mathew, Irina Gorshkova, Wei Zhang, Sekhar P Reddy, Anantha Harijith, Gang Wang, Carol Feghali-Bostwick, Imre Noth, Shwu-Fan Ma, Tong Zhou, Wenli Ma, Joe G N Garcia, and Viswanathan Natarajan.
• Department of Pharmacology, The University of Illinois, Chicago, Illinois, USA.
• Thorax. 2015 Dec 1; 70 (12): 1138-48.

IntroductionIdiopathic 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.MethodsS1P 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.ResultsS1PL 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.ConclusionThese 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/

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