Effect of Smad7 gene overexpression on transforming growth factor beta-induced retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model.

Saika, S ; Yamanaka, O ; et al.

In: Archives of ophthalmology (Chicago, Ill. : 1960), Jg. 125 (2007-05-01), Heft 5, S. 647-54

academicJournal

Objective: To determine the effects of Smad7 gene transfer in the prevention of fibrogenic responses by the retinal pigment epithelium, a major cause of proliferative vitreoretinopathy after retinal detachment, in mice.

Methods: Retinal detachment-induced proliferative vitreoretinopathy in a mouse model. Forty-eight eyes received either an adenoviral gene transfer of Smad7 or Cre recombinase gene only. The eyes were histologically analyzed. A retinal pigment epithelial cell line, ARPE-19, was used to determine whether Smad7 gene transfection suppresses the fibrogenic response to transforming growth factor (TGF) beta2 exposure.

Results: The Smad7 gene transfer inhibited TGF-beta2/Smad signaling in ARPE-19 cells and expression of collagen type I and TGF-beta1 but had no effect on their basal levels. In vivo Smad7 overexpression resulted in suppression of Smad2/3 signals and of the fibrogenic response to epithelial-mesenchymal transition by the retinal pigment epithelium.

Conclusion: Smad7 gene transfer suppresses fibrogenic responses to TGF-beta2 by retinal pigment epithelial cells in vitro and in vivo. Clinical Relevance Smad7 gene transfer might be a new strategy to prevent and treat proliferative vitreoretinopathy.

Titel:	Effect of Smad7 gene overexpression on transforming growth factor beta-induced retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model.
Autor/in / Beteiligte Person:	Saika, S ; Yamanaka, O ; Nishikawa-Ishida, I ; Kitano, A ; Flanders, KC ; Okada, Y ; Ohnishi, Y ; Nakajima, Y ; Ikeda, K
Zeitschrift:	Archives of ophthalmology (Chicago, Ill. : 1960), Jg. 125 (2007-05-01), Heft 5, S. 647-54
Veröffentlichung:	Chicago, IL : American Medical Association, 2007
Medientyp:	academicJournal
ISSN:	0003-9950 (print)
DOI:	10.1001/archopht.125.5.647
Schlagwort:	Adenoviridae genetics Animals Blotting, Western Cell Line Collagen Type I metabolism Fibronectins metabolism Fibrosis Fluorescent Antibody Technique, Indirect Genetic Vectors Mice Pigment Epithelium of Eye drug effects Pigment Epithelium of Eye pathology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transfection Transforming Growth Factor beta1 metabolism Up-Regulation Vitreoretinopathy, Proliferative metabolism Vitreoretinopathy, Proliferative pathology Disease Models, Animal Gene Expression physiology Pigment Epithelium of Eye metabolism Smad7 Protein genetics Transforming Growth Factor beta pharmacology Vitreoretinopathy, Proliferative prevention & control
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Arch Ophthalmol] 2007 May; Vol. 125 (5), pp. 647-54. MeSH Terms: Disease Models, Animal* ; Gene Expression / physiology ; Pigment Epithelium of Eye / metabolism ; Smad7 Protein / genetics ; Transforming Growth Factor beta / pharmacology ; Vitreoretinopathy, Proliferative / *prevention & control ; Adenoviridae / genetics ; Animals ; Blotting, Western ; Cell Line ; Collagen Type I / metabolism ; Fibronectins / metabolism ; Fibrosis ; Fluorescent Antibody Technique, Indirect ; Genetic Vectors ; Mice ; Pigment Epithelium of Eye / drug effects ; Pigment Epithelium of Eye / pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transfection ; Transforming Growth Factor beta1 / metabolism ; Up-Regulation ; Vitreoretinopathy, Proliferative / metabolism ; Vitreoretinopathy, Proliferative / pathology Substance Nomenclature: 0 (Collagen Type I) ; 0 (Fibronectins) ; 0 (Smad7 Protein) ; 0 (Smad7 protein, mouse) ; 0 (Transforming Growth Factor beta) ; 0 (Transforming Growth Factor beta1) Entry Date(s): Date Created: 20070516 Date Completed: 20070605 Latest Revision: 20211110 Update Code: 20231215

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