Regulatory mechanism of human vascular smooth muscle cell phenotypic transformation induced by NELIN

Pei,Changan; Qin,Shiyong; Wang,Minghai; Zhang,Shuguang

doi:10.3892/mmr.2015.4365

November-2015 Volume 12 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

November-2015 Volume 12 Issue 5

Full Size Image

Article Open Access

Regulatory mechanism of human vascular smooth muscle cell phenotypic transformation induced by NELIN

Authors:
- Changan Pei
- Shiyong Qin
- Minghai Wang
- Shuguang Zhang
View Affiliations / Copyright

Affiliations: Department of Vascular Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Vascular Surgery, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China

Copyright: © Pei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 7310-7316
|
Published online on: September 25, 2015

https://doi.org/10.3892/mmr.2015.4365
Expand metrics +

Abstract

Vascular disorders, including hypertension, atherosclerosis and restenosis, arise from dysregulation of vascular smooth muscle cell (VSMC) differentiation, which can be controlled by regulatory factors. The present study investigated the regulatory mechanism of the phenotypic transformation of human VSMCs by NELIN in order to evaluate its potential as a preventive and therapeutic of vascular disorders. An in vitro model of NELIN‑overexpressing VSMCs was prepared by transfection with a lentiviral (LV) vector (NELIN‑VSMCs) and NELIN was slienced using an a lentiviral vector with small interfering (si)RNA in another group (LV‑NELIN‑siRNA‑VSMCs). The effects of NELIN overexpression or knockdown on the phenotypic transformation of human VSMCs were observed, and its regulatory mechanism was studied. Compared with the control group, cells in the NELIN‑VSMCs group presented a contractile phenotype with a significant increase of NELIN mRNA, NELIN protein, smooth muscle (SM)α‑actin and total Ras homolog gene family member A (RhoA) protein expression. The intra‑nuclear translocation of SMα‑actin‑serum response factor (SMα‑actin‑SRF) occurred in these cells simultaneously. Following exposure to Rho kinsase inhibitor Y‑27632, SRF and SMα‑actin expression decreased. However, cells in the LV‑NELIN‑siRNA‑VSMCs group presented a synthetic phenotype, and the expression of NELIN mRNA, NELIN protein, SMα‑actin protein and total RhoA protein was decreased. The occurrence of SRF extra‑nuclear translocation was observed. In conclusion, the present study suggested that NELIN was able to activate regulatory factors of SMα‑actin, RhoA and SRF successively in human VSMCs cultured in vitro. Furthermore, NELIN‑induced phenotypic transformation of human VSMCs was regulated via the RhoA/SRF signaling pathway. The results of the present study provide a foundation for the use of NELIN in preventive and therapeutic treatment of vascular remodeling diseases, including varicosity and atherosclerosis.

View Figures

View References

1	Rzucidlo EM, Martin KA and Powell RJ: Regulation of vascular smooth muscle cell differentiation. J Vasc Surg. 45(Suppl A): A25–A32. 2007. View Article : Google Scholar : PubMed/NCBI
2	Yao QP, Zhang P, Qi YX, et al: The role of SIRT6 in the differentiation of vascular smooth muscle cells in response to cyclic strain. Int J Biochem Cell Biol. 49:98–104. 2014. View Article : Google Scholar : PubMed/NCBI
3	Zhao B, Luo X, Shi H and Ma D: Tissue factor pathway inhibitor-2 is downregulated by ox-LDL and inhibits ox-LDL induced vascular smooth muscle cells proliferation and migration. Thromb Res. 128:179–185. 2011. View Article : Google Scholar : PubMed/NCBI
4	Majesky MW: Developmental basis of vascular smooth muscle diversity. Arterioscl Throm Vas Biol. 27:1248–1258. 2007. View Article : Google Scholar
5	Zhao Y, Wei YJ, Cao HQ and Ding JF: Molecular cloning of NELIN, a putative human cytoskeleton regulation gene. Acta Bioch Bioph Sin. 33:19–24. 2001.
6	Wang Z, Cao HQ, Feng Y, et al: Characteristics of the binding features of Nelin with F-actin and screening Nelin interactive proteins. Chin Sci Bull. 49:2487–2490. 2004.
7	PEI C, QIN S and CHEN S: Effect of Nelin on phenotypic transition of human great saphenous vein smooth muscle cells. Chin J Exp Surg. 30:925–927. 2013.
8	Xu B, Ju Y and Song G: Role of p38, ERK1/2, focal adhesion kinase, RhoA/ROCK and cytoskeleton in the adipogenesis of human mesenchymal stem cells. J Biosci Bioeng. 117:624–631. 2014. View Article : Google Scholar
9	Loirand G, Rolli-Derkinderen M and Pacaud P: RhoA and resistance artery remodeling. Am J Physiol Heart Circ Physiol. 288:H1051–H1056. 2005. View Article : Google Scholar : PubMed/NCBI
10	Rolfe BE, Worth NF, World CJ, Campbell JH and Campbell GR: Rho and vascular disease. Atherosclerosis. 183:1–16. 2005. View Article : Google Scholar : PubMed/NCBI
11	Loirand G, Guérin P and Pacaud P: Rho kinases in cardiovascular physiology and pathophysiology. Circ Res. 98:322–334. 2006. View Article : Google Scholar : PubMed/NCBI
12	Liu HW, Halayko AJ, Fernandes DJ, et al: The RhoA/Rho kinase pathway regulates nuclear localization of serum response factor. Am J Resp Cell Mol Biol. 29:39–47. 2003. View Article : Google Scholar
13	Thormodsson FR and Olafsson IH: Isolation and culturing of human vascular smooth muscle cells. Methods Mol Biol. 299:197–210. 2005.PubMed/NCBI
14	Towbin H, Staehelin T and Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 76:4350–4354. 1979. View Article : Google Scholar : PubMed/NCBI
15	Yu HR, Kuo HC, Huang HC, et al: Glyceraldehyde-3-phosphate dehydrogenase is a reliable internal control in Western blot analysis of leukocyte subpopulations from children. Anal Biochem. 413:24–29. 2011. View Article : Google Scholar : PubMed/NCBI
16	Nagel DJ, Aizawa T, Jeon KI, et al: Role of nuclear Ca2+/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival. Circ Res. 98:777–784. 2006. View Article : Google Scholar : PubMed/NCBI
17	Hirano K: The roles of proteinase-activated receptors in the vascular physiology and pathophysiology. Arterioscl Throm Vas. 27:27–36. 2007. View Article : Google Scholar
18	Pei C and Chen S: Detection of the nelin in peripheral blood of patients with lower extremity varicose veins and its significance. J Shandong Univ Health Sci. 51:64–66. 2013.
19	Yu X and Chen S: Expression and roles of nelin in varicose veins. Chin J Curr Adv Gen Surg. 13:1009–9905. 2010.
20	Morelli A, Chavalmane AK, Filippi S, et al: Atorvastatin ameliorates sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyperactivation. J Sex Med. 6:91–106. 2009. View Article : Google Scholar : PubMed/NCBI
21	Owens GK, Kumar MS and Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 84:767–801. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Regulatory mechanism of human vascular smooth muscle cell phenotypic transformation induced by NELIN

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles