دورية أكاديمية
أعرض في EDS

Exogenous dihydrosphingosine 1 phosphate mediates collagen synthesis in cardiac fibroblasts through JAK/STAT signalling and regulation of TIMP1.

التفاصيل البيبلوغرافية
العنوان: Exogenous dihydrosphingosine 1 phosphate mediates collagen synthesis in cardiac fibroblasts through JAK/STAT signalling and regulation of TIMP1.
المؤلفون: Magaye RR; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia., Savira F; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia., Hua Y; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China., Xiong X; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia; Shanghai Institute of Heart Failure, Research Centre for Translational Medicine, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, China., Huang L; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia., Reid C; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia; School of Public Health School, Curtin University, Perth, Australia., Flynn B; Australian Translational Medicinal Chemistry Facility, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia., Kaye D; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia., Liew D; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia., Wang BH; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in therapeutics, Melbourne, Australia. Electronic address: bing.wang@baker.edu.au.
المصدر: Cellular signalling [Cell Signal] 2020 Aug; Vol. 72, pp. 109629. Date of Electronic Publication: 2020 Apr 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 8904683 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3913 (Electronic) Linking ISSN: 08986568 NLM ISO Abbreviation: Cell Signal Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science Ltd
Original Publication: Oxford ; New York : Pergamon Press, 1988-
مواضيع طبية MeSH: Signal Transduction*/drug effects, Collagen/*biosynthesis , Fibroblasts/*metabolism , Janus Kinases/*metabolism , Myocardium/*cytology , STAT Transcription Factors/*metabolism , Sphingosine/*analogs & derivatives , Tissue Inhibitor of Metalloproteinase-1/*metabolism, Animals ; Animals, Newborn ; Biomarkers/metabolism ; Cell Differentiation/drug effects ; Fibroblasts/drug effects ; Gene Expression Regulation/drug effects ; Hypertrophy ; Janus Kinases/antagonists & inhibitors ; Lysophospholipids/pharmacology ; Matrix Metalloproteinase 2/metabolism ; Models, Biological ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Oxadiazoles/pharmacology ; Phosphorylation/drug effects ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats, Sprague-Dawley ; Smad2 Protein/metabolism ; Sphingosine/pharmacology ; Thiophenes/pharmacology ; Time Factors ; Transforming Growth Factor beta/metabolism
مستخلص: Cardiac fibrosis and myocyte hypertrophy are hallmarks of the cardiac remodelling process in cardiomyopathies such as heart failure (HF). Dyslipidemia or dysregulation of lipids contribute to HF. The dysregulation of high density lipoproteins (HDL) could lead to altered levels of other lipid metabolites that are bound to it such as sphingosine-1- phosphate (S1P). Recently, it has been shown that S1P and its analogue dihydrosphingosine-1-phosphate (dhS1P) are bound to HDL in plasma. The effects of dhS1P on cardiac cells have been obscure. In this study, we show that extracellular dhS1P is able to increase collagen synthesis in neonatal rat cardiac fibroblasts (NCFs) and cause hypertrophy of neonatal cardiac myocytes (NCMs). The janus kinase/signal transducer and activator (JAK/STAT) signalling pathway was involved in the increased collagen synthesis by dhS1P, through sustained increase of tissue inhibitor of matrix metalloproteinase 1 (TIMP1). Extracellular dhS1P increased phosphorylation levels of STAT1 and STAT3 proteins, also caused an early increase in gene expression of transforming growth factor-β (TGFβ), and sustained increase in TIMP1. Inhibition of JAKs led to inhibition of TIMP1 and TGFβ gene and protein expression. We also show that dhS1P is able to cause NCM hypertrophy through S1P-receptor-1 (S1PR1) signalling which is opposite to that of its analogue, S1P. Taken together, our results show that dhS1P increases collagen synthesis in cardiac fibroblasts causing fibrosis through dhS1P-JAK/STAT-TIMP1 signalling.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Cardiac remodelling; Dihydropshingosine 1 phosphate; JAK/STAT signalling; Sphingolipid; TIMP1
المشرفين على المادة: 0 (Biomarkers)
0 (Lysophospholipids)
0 (Oxadiazoles)
0 (RNA, Messenger)
0 (SEW2871)
0 (STAT Transcription Factors)
0 (Smad2 Protein)
0 (Thiophenes)
0 (Tissue Inhibitor of Metalloproteinase-1)
0 (Transforming Growth Factor beta)
19794-97-9 (dihydrosphingosine 1-phosphate)
26993-30-6 (sphingosine 1-phosphate)
9007-34-5 (Collagen)
EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
EC 2.7.1.- (sphingosine kinase)
EC 2.7.10.2 (Janus Kinases)
EC 3.4.24.24 (Matrix Metalloproteinase 2)
NGZ37HRE42 (Sphingosine)
تواريخ الأحداث: Date Created: 20200412 Date Completed: 20210803 Latest Revision: 20210803
رمز التحديث: 20221213
DOI: 10.1016/j.cellsig.2020.109629
PMID: 32278008
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-3913
DOI:10.1016/j.cellsig.2020.109629