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Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3/Cathepsin S Signaling Pathway
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 17, p 4202 (2019), Volume 20, Issue 17
- Publication Year :
- 2019
-
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 &beta<br />glycerophosphate (&beta<br />GP). The experiments showed that NaHS (an H2S donor, 100 &mu<br />M) 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&alpha<br />actin and SM22&alpha<br />two phenotypic markers of smooth muscle cells, and decreasing core binding factor &alpha<br />1 (Cbf&alpha<br />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.
- Subjects :
- 0301 basic medicine
hydrogen sulfide
Endogeny
030204 cardiovascular system & hematology
Muscle, Smooth, Vascular
lcsh:Chemistry
calcification
0302 clinical medicine
STAT3
lcsh:QH301-705.5
Spectroscopy
Cells, Cultured
Cathepsin S
biology
Chemistry
Phosphorus
General Medicine
Computer Science Applications
Cell biology
smooth muscle cells
cathepsin S
cardiovascular system
Signal transduction
Signal Transduction
STAT3 Transcription Factor
Myocytes, Smooth Muscle
chemistry.chemical_element
elastin
Calcium
Sulfides
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
medicine
Humans
Physical and Theoretical Chemistry
Vascular Calcification
Molecular Biology
Stat3
Organic Chemistry
Wild type
medicine.disease
Cathepsins
030104 developmental biology
Glucose
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Elastin
Calcification
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 20
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....469c92da14e517dcfcc12d9052a9c60a