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Plasmid-based short hairpin RNA against connective tissue growth factor attenuated monocrotaline-induced pulmonary vascular remodeling in rats

Gene Therapy volume 21, pages 931–937 (2014)Cite this article

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Abstract

Pulmonary hypertension is a life-threatening medical condition, and a growing body of evidence shows that the expression of connective tissue growth factor (CTGF) is significantly associated with its pathogenesis, making it an attractive therapeutic target. Our earlier work revealed that plasmid-based CTGF-specific short hairpin RNA (shRNA) could attenuate pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in rats exposed to cigarette smoke. In this study, we explored the therapeutic role of this shRNA plasmid in the treatment of monocrotaline-induced pulmonary vascular remodeling in rats, and demonstrated that the upregulation of CTGF in PASMCs following a single injection of monocrotaline could be attenuated by administration of the shRNA. Accordingly, this shRNA was found to repress monocrotaline-induced pulmonary vascular remodeling, as evidenced by its ability to reduce the percentage of muscularized vessels and the wall thickness of pulmonary vessels. We concluded that plasmid-based shRNA against CTGF attenuated pulmonary vascular remodeling in monocrotaline-treated rats. CTGF might be a potential target for the treatment of pulmonary vascular remodeling and pulmonary hypertension.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81300041, 81100038), the Natural Science Foundation of the Anhui Higher Education Institutions of China (KJ2012Z184), fund for the academic backbone of the excellent young and middle-aged people of Anhui Medical University (2013) and fund for reserve talents of the First Affiliated Hospital of Anhui Medical University (2014).

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  1. R Wang and S-j Zhou: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China

    R Wang, S-j Zhou, R Xu, L-m Fei, Q-q Zhu, Y Zhang & G-y Sun

  2. Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, People’s Republic of China

    S-j Zhou

  3. Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China

    D-x Zeng

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  1. R Wang
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Correspondence to G-y Sun.

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Wang, R., Zhou, Sj., Zeng, Dx. et al. Plasmid-based short hairpin RNA against connective tissue growth factor attenuated monocrotaline-induced pulmonary vascular remodeling in rats. Gene Ther 21, 931–937 (2014). https://doi.org/10.1038/gt.2014.62

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