HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/C282    most recent 00306.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Saika, S. Articles by Ooshima, A. Search for Related Content PubMed PubMed Citation Articles by Saika, S. Articles by Ooshima, A.

RECEPTORS AND SIGNAL TRANSDUCTION

Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-to-mesenchymal transition of lens epithelium in mice

Departments of ¹Ophthalmology and ²Pathology, Wakayama Medical University, Wakayama; Department of ³Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan; and ⁴Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Submitted 27 June 2005 ; accepted in final form 17 August 2005

We have examined the effect of adenovirus-mediated expression of bone morphogenic protein-7 (BMP-7) and inhibitors of differentiation 2 and 3 (Id2 and Id3) on injury-induced epithelial-to-mesenchymal transition (EMT) of lens epithelium in mice. Id2 and Id3 are known to be upregulated by BMP-7 and to antagonize Smad2/3 signaling. The Cre-LoxP system adenoviral gene transfer was used. Three microliters of adenoviral solution (2 x 10⁷ PFU/µl) were injected into the right lens of adult male C57BL/6 mice (n = 144) at the time of capsular injury induced using a hypodermic needle under both general and topical anesthesia. A mixture of Cre-adenovirus (Cre-Ad) and vector encoding mBMP-7, mId2, or mId3 was administered in a test group. Control lenses were treated with Cre-Ad alone. After healing intervals of 5 or 10 days, the animals were killed and then we performed histological processes or RNA extraction from the lens. RT-PCR, real-time RT-PCR, and immunohistochemistry showed expression of each introduced gene in the lens. Exogenous BMP-7 upregulated expression of Id2 and Id3 in injured lenses, and gene introduction of Id2 or Id3 also upregulated BMP-7 expression. Gene transfer of BMP-7, Id2, or Id3 delayed injury-induced EMT of the lens epithelial cells as evaluated by histology and expression patterns of -smooth muscle actin and collagens in association with reduction of Smad2 COOH-terminal phosphorylation. Gene transfer of BMP-7, Id2, or Id3 delayed injury-induced EMT of lens epithelial cells and subsequent sealing of the capsular break with fibrous tissue in mice.

lens epithelial cell; bone morphogenic protein-7; inhibitor of differentiation; Smad

This article has been cited by other articles:

				A. Kitano, S. Saika, O. Yamanaka, K. Ikeda, Y. Okada, K. Shirai, and P. S. Reinach Emodin Suppression of Ocular Surface Inflammatory Reaction Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5013 - 5022. [Abstract] [Full Text] [PDF]

				B. C. Willis and Z. Borok TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L525 - L534. [Abstract] [Full Text] [PDF]

				S. Saika, O. Yamanaka, I. Nishikawa-Ishida, A. Kitano, K. C. Flanders, Y. Okada, Y. Ohnishi, Y. Nakajima, and K. Ikeda Effect of Smad7 Gene Overexpression on Transforming Growth Factor beta-Induced Retinal Pigment Fibrosis in a Proliferative Vitreoretinopathy Mouse Model Arch Ophthalmol, May 1, 2007; 125(5): 647 - 654. [Abstract] [Full Text] [PDF]

				N. W. Morrell Pulmonary Hypertension Due to BMPR2 Mutation: A New Paradigm for Tissue Remodeling? Proceedings of the ATS, November 1, 2006; 3(8): 680 - 686. [Abstract] [Full Text] [PDF]