Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. Issue 12 (18th August 2015)

• Record Type: Journal Article
• Authors: Huang, Long Shuang; Berdyshev, Evgeny V; Tran, John T; Xie, Lishi; Chen, Jiwang; Ebenezer, David L; Mathew, Biji; Gorshkova, Irina; Zhang, Wei; Reddy, Sekhar P; Harijith, Anantha; Wang, Gang; Feghali-Bostwick, Carol; Noth, Imre; Ma, Shwu-Fan; Zhou, Tong; Ma, Wenli; Garcia, Joe G N; Natarajan, Viswanathan
• Is Part Of: Thorax. Volume 70:Issue 12(2015)
• Page Start: 1138
• Page End: 1148
• Publication Date: 2015-08-18
• Subjects: Idiopathic pulmonary fibrosis; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2014-206684
• Languages: English
• ISSNs: 0040-6376

Abstract

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.