Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix.

Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Research Abstract Details 

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Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Abstract Text:

Adriana J LaGier,Sonia H Yoo,Eduardo C Alfonso,Sally Meiners,M Elizabeth Fini,

PURPOSE: Transforming growth factor (TGF)-beta2 is a major epithelial mediator of fibrotic marker expression during corneal repair in mice. Production of TGF-beta2 protein by cultured rabbit corneal epithelial cells is reduced by plating on a basement membrane-like extracellular matrix extract (Matrigel; BD Biosciences, Bedford, MA). The goal of the present study was to understand further the nature of Matrigel regulation. METHODS: TGF-beta2 protein, mRNA, and gene transcriptional promotion were characterized in cultured human corneal epithelial cells. RESULTS: TGF-beta2 production was inhibited by Matrigel at the level of mRNA accumulation and activity of the gene transcriptional promoter. This effect of Matrigel was not explained by (1) growth factor contaminants, as growth-factor reduced Matrigel also inhibited TGF-beta2; (2) independent matrix components, as the pure forms of the major ECM components laminin and collagen IV did not reproduce the effect; or (3) inhibition of a constitutive TGF-beta2 autocrine feedback loop, as addition of exogenous TGF-beta2 increased p-Smad3 and restored TGF-beta2 mRNA levels. In addition, Matrigel's ability to reduce TGF-beta2 was not explained by its geometry, as TGF-beta2 production was not inhibited by plating cells on a synthetic nanofiber matrix with a three-dimensional topography similar to Matrigel. Matrigel caused a reduction of ezrin, a member of the ezrin-radixin-moesin (ERM) family, which plays a role in establishing polarity of epithelial cells in tissues through the Rho signaling pathway. CONCLUSIONS: These findings indicate that Matrigel inhibits TGF-beta2 gene expression and point to a mechanism dependent on Matrigel composition and structure. The capacity of Matrigel to reduce ezrin is consistent with this idea and directs the focus of future studies toward the ERM/Rho pathway.

Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Publishing Authors By Initials

AJ LaGier,SH Yoo,EC Alfonso,S Meiners,ME Fini,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta2 research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta2 research

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Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Investigative ophthalmology & visual science

VOLUME: 48

Page Numbers: 1061-71

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 3

MONTH: Mar

YEAR: 2007

Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7703701

Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta2

MESH TERMS: genetics

Chemical & Substance for Abstract: Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix. Information

Substance Name: Collagen

Registry Number: 9007-34-5

Grant and Affiliation Information for Inhibition of human corneal epithelial production of fibrotic mediator TGF-beta2 by basement membrane-like extracellular matrix.

AFFILIATION: Evelyn F. and William L. McKnight Vision Research Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY014801

ACRONYM: EY

MEDLINETA: Invest Ophthalmol Vis Sci

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