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Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2018; Vol. 46 (4), pp. 1305-1316. Date of Electronic Publication: 2018 Apr 18. - Publication Year :
- 2018
-
Abstract
- Background/aims: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification.<br />Methods: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress.<br />Results: Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide.<br />Conclusions: Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.<br /> (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Subjects :
- Alkaline Phosphatase genetics
Alkaline Phosphatase metabolism
Cell Line
Cell Transdifferentiation drug effects
Chondrogenesis drug effects
Core Binding Factor Alpha 1 Subunit genetics
Core Binding Factor Alpha 1 Subunit metabolism
Extracellular Matrix Proteins genetics
Extracellular Matrix Proteins metabolism
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Hydrogen Peroxide toxicity
Matrix Metalloproteinase 2 genetics
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 genetics
Matrix Metalloproteinase 9 metabolism
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular metabolism
NADPH Oxidase 4 genetics
NADPH Oxidase 4 metabolism
Osteogenesis drug effects
Plasminogen Activator Inhibitor 1 genetics
Plasminogen Activator Inhibitor 1 metabolism
Recombinant Proteins biosynthesis
Recombinant Proteins isolation & purification
Recombinant Proteins pharmacology
SOX9 Transcription Factor genetics
SOX9 Transcription Factor metabolism
Calcification, Physiologic drug effects
Extracellular Matrix Proteins pharmacology
Glycerophosphates pharmacology
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 46
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29689558
- Full Text :
- https://doi.org/10.1159/000489144