Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts
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) hav...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264607/ https://www.ncbi.nlm.nih.gov/pubmed/34277924 http://dx.doi.org/10.1016/j.ijcha.2021.100837 |
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author | Magaye, Ruth R. Savira, Feby Xiong, Xin Huynh, Kevin Meikle, Peter J. Reid, Christopher Flynn, Bernard L. Kaye, David Liew, Danny Wang, Bing H. |
author_facet | Magaye, Ruth R. Savira, Feby Xiong, Xin Huynh, Kevin Meikle, Peter J. Reid, Christopher Flynn, Bernard L. Kaye, David Liew, Danny Wang, Bing H. |
author_sort | Magaye, Ruth R. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8264607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82646072021-07-16 Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts Magaye, Ruth R. Savira, Feby Xiong, Xin Huynh, Kevin Meikle, Peter J. Reid, Christopher Flynn, Bernard L. Kaye, David Liew, Danny Wang, Bing H. Int J Cardiol Heart Vasc Original Paper 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. Elsevier 2021-07-06 /pmc/articles/PMC8264607/ /pubmed/34277924 http://dx.doi.org/10.1016/j.ijcha.2021.100837 Text en © 2021 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Paper Magaye, Ruth R. Savira, Feby Xiong, Xin Huynh, Kevin Meikle, Peter J. Reid, Christopher Flynn, Bernard L. Kaye, David Liew, Danny Wang, Bing H. Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title | Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title_full | Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title_fullStr | Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title_full_unstemmed | Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title_short | Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts |
title_sort | dihydrosphingosine driven enrichment of sphingolipids attenuates tgfβ induced collagen synthesis in cardiac fibroblasts |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264607/ https://www.ncbi.nlm.nih.gov/pubmed/34277924 http://dx.doi.org/10.1016/j.ijcha.2021.100837 |
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