Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts

International Journal of Cardiology: Heart & Vasculature

Kevin Huynh¹  Feby Savira¹  Christopher Reid¹  Bing H. Wang²  Bernard L. Flynn³  Xin Xiong⁴  Peter J. Meikle⁴  Ruth R. Magaye⁴  Danny Liew⁵  David Kaye⁵ 

[1] Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia;School of Public Health School, Curtin University, Perth, Australia;Shanghai Institute of Heart Failure, Research Centre for Translational Medicine, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, PR China;Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia;Metabolomics Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia;

关键词: Cardiac fibroblasts;    Collagen synthesis;    Dihydrosphingosine;    Sphingolipid;    TGFβ;   

DOI  :  

来源: DOAJ

【 摘 要 】

The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor β (TGFβ). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.

【 授权许可】

Unknown