International Journal of Medical Sciences

Impact factor
2.399

17 December 2017

ISSN 1449-1907 News feeds of published articles

My Manuscript | My Account

Journal of Biomedicinenew

Theranostics

Journal of Cancer

Oncomedicine

International Journal of Biological Sciences

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

PubMed Central Indexed in Journal Impact Factor

Int J Med Sci 2013; 10(12):1702-1714. doi:10.7150/ijms.7114

Research Paper

Airway Administration of Vascular Endothelial Growth Factor siRNAs Induces Transient Airspace Enlargement in Mice

Yusuke Takahashi1, Yotaro Izumi1✉, Mitsutomo Kohno1, Eiji Ikeda2, Hiroaki Nomori1

1. Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
2. Department of Pathology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

Abstract

Purpose: Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice.

Methods: Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry.

Results: Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression.

Conclusions: The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.

Keywords: vascular endothelial growth factor, emphysema, mouse model.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Takahashi Y, Izumi Y, Kohno M, Ikeda E, Nomori H. Airway Administration of Vascular Endothelial Growth Factor siRNAs Induces Transient Airspace Enlargement in Mice. Int J Med Sci 2013; 10(12):1702-1714. doi:10.7150/ijms.7114. Available from http://www.medsci.org/v10p1702.htm