Nucleolin promotes Ang II‑induced phenotypic transformation of vascular smooth muscle cells via interaction with tropoelastin mRNA

Fang,Li; Zhang,Peng‑Fei; Wang,Kang‑Kai; Xiao,Zhi‑Lin; Yang,Mei; Yu,Zai‑Xin

doi:10.3892/ijmm.2019.4090

Nucleolin promotes Ang II‑induced phenotypic transformation of vascular smooth muscle cells via interaction with tropoelastin mRNA

Authors:
- Li Fang
- Peng‑Fei Zhang
- Kang‑Kai Wang
- Zhi‑Lin Xiao
- Mei Yang
- Zai‑Xin Yu
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Affiliations: Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China, Department of Geriatric Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: February 4, 2019 https://doi.org/10.3892/ijmm.2019.4090
Pages: 1597-1610
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The current study aimed to clarify the role of nucleolin in the phenotypic transformation of vascular smooth muscle cells (VSMCs) and to preliminarily explore its underlying mechanism. The spatial and temporal expression patterns of nucleolin, and the effects of angiotensin II (Ang II) on the expression of VSMC phenotypic transformation markers, α‑smooth muscle‑actin, calponin, smooth muscle protein 22α and osteopontin were investigated. The effects of nucleolin on VSMC phenotypic transformation and the expression of phenotypic transformation‑associated genes, tropoelastin, epiregulin and fibroblast growth factor 2 (b‑FGF), were determined. Protein‑RNA co‑immunoprecipitation was used to investigate the potential target genes regulated by the nucleolin in phenotypic transformation of VSMCs. Finally, the stability of tropoelastin mRNA and the effects of nucleolin on the expression of tropoelastin were assayed. The results revealed that Ang II significantly promoted the phenotypic transformation of VSMCs. The expression of nucleolin was gradually upregulated in VSMCs treated with Ang II at different concentrations for various durations. Ang II induced nucleolin translocation from the nucleus to cytoplasm. Additionally, Ang II significantly promoted the phenotypic transformation of VSMCs. Overexpression and silencing of nucleolin regulated the expressions of tropoelastin, epiregulin and b‑FGF. There was an interaction between tropoelastin mRNA and nucleolin protein, promoting the stability of tropoelastin mRNA and enhancing the expression of tropoelastin at the protein level. Upregulation of nucleolin had an important role in Ang II‑induced VSMC phenotypic transformation, and its underlying mechanism may be through interacting with tropoelastin mRNA, leading to its increased stability and protein expression. The findings provide a new perspective into the regulatory mechanism of VSMC phenotypic transformation.

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