dc.contributor.author
Boehme, Beate
dc.contributor.author
Schelski, Nadeshda
dc.contributor.author
Makridakis, Manousos
dc.contributor.author
Henze, Laura
dc.contributor.author
Vlahou, Antonia
dc.contributor.author
Lang, Florian
dc.contributor.author
Pieske, Burkert
dc.contributor.author
Alesutan, Ioana
dc.contributor.author
Voelkl, Jakob
dc.date.accessioned
2019-04-23T12:09:02Z
dc.date.available
2019-04-23T12:09:02Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24474
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2245
dc.description.abstract
Background/Aims: Hyperphosphatemia promotes medial vascular calcification, at least partly, by induction of osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). The complex signaling pathways regulating this process are still incompletely understood. The present study investigated the role of cytosolic serine hydroxymethyl transferase 1 (SHMT1) in phosphate-induced vascular calcification. Methods: Endogenous expression of SHMT1 was suppressed by silencing in primary human aortic smooth muscle cells (HAoSMCs) followed by treatment without and with phosphate or antioxidants. Results: In HAoSMCs, SHMT1 mRNA expression was up-regulated by phosphate. Silencing of SHMT1 alone was sufficient to induce osteo-/chondrogenic transdifferentiation of HAoSMCs, as shown by increased tissue-nonspecific alkaline phosphatase (ALPL) activity and osteogenic markers MSX2, CBFA1 and ALPL mRNA expression. Furthermore, phosphate-induced ALPL mRNA expression and activity as well as calcification were augmented in SHMT1 silenced HAoSMCs as compared to negative control siRNA transfected HAoSMCs. Silencing of SHMT1 decreased total antioxidant capacity and up-regulated NADH/NADPH oxidase system components NOX4 and CYBA mRNA expression in HAoSMCs, effects paralleled by increased mRNA expression of matrix metalloproteinase MMP2 as well as BAX/BCL2 ratio. More importantly, additional treatment with antioxidants TEMPOL or TIRON blunted the increased osteogenic markers mRNA expression in SHMT1 silenced HAoSMCs. Conclusion: Silencing of SHMT1 promotes osteo-/chondrogenic signaling in VSMCs, at least in part, by inducing cellular oxidative stress. It thus aggravates phosphate-induced calcification of VSMCs. The present findings support a regulatory role of SHMT1 in vascular calcification during conditions of hyperphosphatemia such as chronic kidney disease. (C) 2018 The Author(s) Published by S. Karger AG, Basel
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Oxidative stress
en
dc.subject
Vascular calcification
en
dc.subject
Osteo-/chondrogenic signaling
en
dc.subject
Vascular smooth muscle cells
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate- Induced Vascular Smooth Muscle Cell Calcification
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1159/000492248
dcterms.bibliographicCitation.journaltitle
Kidney & Blood Pressure Research
dcterms.bibliographicCitation.number
4
dcterms.bibliographicCitation.originalpublishername
Karger Publishers
dcterms.bibliographicCitation.pagestart
1212
dcterms.bibliographicCitation.pageend
1221
dcterms.bibliographicCitation.volume
43
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30071536
dcterms.isPartOf.issn
1420-4096