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Bone Morphogenetic Protein-4 Promotes Phenotypic Modulation via SMAD-4/MCT-4 Axis in Vascular Smooth Muscle Cells.
- Source :
-
Journal of vascular research [J Vasc Res] 2024; Vol. 61 (3), pp. 99-108. Date of Electronic Publication: 2023 Dec 27. - Publication Year :
- 2024
-
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).<br />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.<br />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.<br />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.<br /> (© 2023 S. Karger AG, Basel.)
- Subjects :
- Animals
Humans
Male
Cells, Cultured
Lactic Acid metabolism
Lactic Acid blood
Angioplasty, Balloon adverse effects
Vascular System Injuries pathology
Vascular System Injuries metabolism
Vascular System Injuries genetics
Cell Plasticity drug effects
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Muscle, Smooth, Vascular drug effects
Myocytes, Smooth Muscle metabolism
Myocytes, Smooth Muscle pathology
Myocytes, Smooth Muscle drug effects
Phenotype
Signal Transduction
Bone Morphogenetic Protein 4 metabolism
Bone Morphogenetic Protein 4 genetics
Rats, Sprague-Dawley
Smad4 Protein metabolism
Smad4 Protein genetics
Cell Movement drug effects
Neointima
Disease Models, Animal
Hyperplasia
Monocarboxylic Acid Transporters metabolism
Monocarboxylic Acid Transporters genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0135
- Volume :
- 61
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of vascular research
- Publication Type :
- Academic Journal
- Accession number :
- 38151007
- Full Text :
- https://doi.org/10.1159/000532029