Avβ3 Single-Stranded DNA Aptamer Attenuates Vascular Smooth Muscle Cell Proliferation and Migration via Ras-PI3K/MAPK Pathway

Autor: Luocheng Li, Hongbing Wu, Feng Shi, Rui Hu, Zongli Ren, Zhiwei Wang, Xiaoping Hu, Bowen Li
Rok vydání: 2020
Předmět:
0301 basic medicine
MAPK/ERK pathway
Vascular smooth muscle
Article Subject
Myocytes
Smooth Muscle
Integrin
DNA
Single-Stranded
Apoptosis
RM1-950
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Movement
Animals
Diseases of the circulatory (Cardiovascular) system
Myocyte
Medicine
Pharmacology (medical)
Phosphorylation
Cells
Cultured
PI3K/AKT/mTOR pathway
Cell Proliferation
Pharmacology
biology
Cell growth
business.industry
General Medicine
Aptamers
Nucleotide
Integrin alphaVbeta3
Cell biology
030104 developmental biology
Gene Expression Regulation
Focal Adhesion Kinase 1
RC666-701
030220 oncology & carcinogenesis
ras Proteins
biology.protein
Osteopontin
Therapeutics. Pharmacology
Mitogen-Activated Protein Kinases
Signal transduction
Apoptosis Regulatory Proteins
Cardiology and Cardiovascular Medicine
business
Research Article
Signal Transduction
Zdroj: Cardiovascular Therapeutics, Vol 2020 (2020)
Cardiovascular Therapeutics
ISSN: 1755-5922
1755-5914
DOI: 10.1155/2020/6869856
Popis: Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism.Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs.Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot.Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P<0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P<0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P<0.05).Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.
Databáze: OpenAIRE
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