Inhibition of vascular calcification by microRNA-155-5p is accompanied by the inactivation of TGF-β1/Smad2/3 signaling pathway.

Abstract

Vascular calcification (VC) is a vital factor for cardiovascular morbidity and mortality. Accumulating data suggest that microRNA (miR) is implicated in the VC. The main purpose of this study is to study the influence of miR-155-5p overexpression on VC development in vitro and in vivo. Immunofluorescence staining, real-time PCR, alizarin red staining, alkaline phosphatase (ALP) activity assay, western blot, luciferase assay, hematoxylin-eosin (HE), Masson's trichrome staining, and calcium content assay were used in this research. The results showed that miR-155-5p was decreased in the rat vascular smooth muscle cells (rVSMCs) undergoing calcification in vitro. MiR-155-5p overexpression reversed the increase of calcification and ALP activity in calcified cells. Further, overexpression of miR-155-5p inhibited the transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway, as evidenced by decreased protein expression of TGF-β1, pSmad-2 and pSmad-3 in rVSMCs. MiR-155-5p was showed to target Smad2 directly. Moreover, miR-155-5p upregulation reduced vascular thickening, fibrosis and calcium content of aorta abdominalis in CaCl2-mediated VC model. Collectively, our results suggest that miR-155-5p overexpression may inhibit VC development through suppressing TGF-β1/Smad2/3 signaling pathway in vivo and in vitro, indicating that miR-155-5p may act as a potential therapeutic target for VC-related disease.

• Authors: Fali Zhao, Yi Wu, Wei Yang, Dongdong Wu, Can Wang, Fengmin Zhang
• Journal: Acta histochemica (Acta Histochem) Vol. 122 Issue 4 Pg. 151551 (May 2020) ISSN: 1618-0372 [Electronic] Germany
• PMID: 32345535 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier GmbH. All rights reserved.

Chemical References

• MIRN155 microRNA, rat
• MicroRNAs
• Smad2 Protein
• Smad2 protein, rat
• Smad3 Protein
• Smad3 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Alkaline Phosphatase
• Calcium Chloride
• Calcium

Topics

• Alkaline Phosphatase (metabolism)
• Animals
• Calcinosis (chemically induced, genetics, pathology)
• Calcium (metabolism)
• Calcium Chloride
• Fibrosis (pathology)
• Male
• MicroRNAs (genetics)
• Myocytes, Smooth Muscle (pathology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (genetics)
• Smad2 Protein (genetics)
• Smad3 Protein (genetics)
• Transforming Growth Factor beta1 (genetics)