Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms20174202
Title: Hydrogen sulfide prevents elastin loss and attenuates calcification induced by high glucose in smooth muscle cells through suppression of stat3/cathepsin s signaling pathway
Authors: Zhou, Y.-B. 
Zhou, H.
Li, L.
Kang, Y.
Cao, X. 
Wu, Z.-Y. 
Ding, L.
Sethi, G. 
Bian, J.-S. 
Keywords: Calcification
Cathepsin S
Elastin
Hydrogen sulfide
Smooth muscle cells
Stat3
Issue Date: 2019
Publisher: MDPI AG
Citation: Zhou, Y.-B., Zhou, H., Li, L., Kang, Y., Cao, X., Wu, Z.-Y., Ding, L., Sethi, G., Bian, J.-S. (2019). Hydrogen sulfide prevents elastin loss and attenuates calcification induced by high glucose in smooth muscle cells through suppression of stat3/cathepsin s signaling pathway. International Journal of Molecular Sciences 20 (17) : 4202. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms20174202
Rights: Attribution 4.0 International
Abstract: Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial calcification (AMC) that is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, can prevent elastin loss and attenuate calcification induced by high glucose in SMCs. Calcification was induced by high glucose (4500 mg/L) in human aortic SMCs (HASMCs) under the condition of calcifying medium containing 10 mM ?-glycerophosphate (?-GP). The experiments showed that NaHS (an H2S donor, 100 µM) mitigated the calcification of HASMCs treated with high glucose by decreasing calcium and phosphorus levels, calcium deposition and ALP activity and inhibited osteogenic transformation by increasing SM?-actin and SM22?, two phenotypic markers of smooth muscle cells, and decreasing core binding factor ?-1 (Cbf?-1), a key factor in bone formation, protein expressions in HASMCs. Moreover, NaHS administration inhibited the activation of Stat3, cathepsin S (CAS) activity and its expression, but increased the level of elastin protein. Pharmacological inhibition or gene silencing Stat3 not only reversed elastin loss, but also attenuated CAS expression. Inhibition of CAS alleviated, while CAS overexpression exacerbated, elastin loss. Interestingly, overexpression of wild type (WT)-Stat3, but not its mutant C259S, elevated CAS protein expression and reduced elastin level. Moreover, NaHS induced S-sulfhydration in WT, but not in the C259S Stat3. These data suggest that H2S may directly regulate Cys259 residue in Stat3 and then impair its signaling function. Our data indicate that H2S may attenuate vascular calcification by upregulating elastin level through the inhibition of Stat3/CAS signaling. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/209551
ISSN: 1661-6596
DOI: 10.3390/ijms20174202
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_3390_ijms20174202.pdf5.45 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

23
checked on Jan 25, 2023

Page view(s)

76
checked on Jan 26, 2023

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons