SPARC induces phenotypic modulation of human brain vascular smooth muscle cells via AMPK/mTOR-mediated autophagy.
Neurosci Lett
; 712: 134485, 2019 11 01.
Article
en En
| MEDLINE
| ID: mdl-31499136
ABSTRACT
Secreted protein acidic and rich in cysteine (SPARC) was widely expressed in VSMCs of human IAs and could reduce the capability of self-repair. This indicates that SPARC may play a role in the promotion of IAs formation and progression, but the mechanism remains unclear. In this study, we further investigated whether SPARC could induce phenotypic modulation of Human Brain Vascular Smooth Muscle Cells (HBVSMCs) and sought to elucidate the role of SPARC-mediated autophagy involved in it. The results demonstrated that SPARC inhibited the expression of contractile genes in HBVSMCs and induced a synthetic phenotype. More importantly, SPARC significantly up-regulated multiple proteins including autophagy marker microtubule-associated protein light chain 3-II (LC3-II), Beclin-1, and autophagy-related gene 5(ATG5). Furthermore, SPARC could promote p62 degradation. The autophagy inhibitor 3- methyladenine (3-MA) significantly blocked SPARC-induced phenotypic modulation of HBVSMCs. We further sought to elucidate the molecular mechanism involved in SPARC-induced autophagy, and found that SPARC could activate the AMPK/mTOR signaling pathway in HBVSMCs. AMPK could be pharmacologically inhibited by Compound C (CC), which significantly decreased the phosphorylation of AMPK into p-AMPK, increased the phosphorylation of mTOR into p-mTOR, and decreased LC3-II, Beclin-1 and ATG5 levels. This suggested that activated AMPK/ mTOR signaling is related to SPARC-mediated autophagy. These results indicated that SPARC plays a role in the phenotypic modulation of HBVSMCs through autophagy activation by AMPK/mTOR signaling pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Encéfalo
/
Osteonectina
/
Adenilato Quinasa
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Miocitos del Músculo Liso
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Serina-Treonina Quinasas TOR
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Músculo Liso Vascular
Límite:
Humans
Idioma:
En
Revista:
Neurosci Lett
Año:
2019
Tipo del documento:
Article