Bone Morphogenetic Protein-4 Promotes Phenotypic Modulation via SMAD-4/MCT-4 Axis in Vascular Smooth Muscle Cells.
J Vasc Res
; 61(3): 99-108, 2024.
Article
em En
| MEDLINE
| ID: mdl-38151007
ABSTRACT
INTRODUCTION:
This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs).METHODS:
Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured. Protein and mRNA expression levels were detected through Western blot and real-time PCR. Cell migration was measured by transwell assay.RESULTS:
Our data showed that serum concentration of BMP-4 was upregulated after balloon injury. Treatment with BMP-4 inhibitor DMH1 (4-(6-(4-isopropoxyphenyl)pyrazolo(1,5-a)pyrimidin-3-yl)quinoline) suppressed the abnormal expression of BMP-4 and inhibited the intimal hyperplasia induced by balloon injury. Compared to BMP-4-negative medium, BMP-4-positive medium was associated with higher synthetic VSMC marker expression levels and lower in contractile gene markers in cultured HA-SMCs. Transfection of monocarboxylic acid transporters-4 (MCT-4) siRNA inhibited the excretion of lactate induced by BMP-4.CONCLUSION:
Our analyses provided evidence that BMP-4 and its regulator Smad-4 are key regulators in MCT-4-mediated lactate excretion. This indicates that BMP-4 stimulates the phenotypic transition of VSMCs via SMAD-4/MCT-4 signaling pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Transdução de Sinais
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Movimento Celular
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Ratos Sprague-Dawley
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Transportadores de Ácidos Monocarboxílicos
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Miócitos de Músculo Liso
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Modelos Animais de Doenças
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Proteína Smad4
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Proteína Morfogenética Óssea 4
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Neointima
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Vasc Res
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China