May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
The Regulation of NADPH Oxidase by TGF–ß in Epithelial Cells
Author Affiliations & Notes
  • M.–J. Son
    Lab, Catholic, Seoul, Republic of Korea
  • C.–K. Joo
    Lab, Catholic, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  M. Son, None; C. Joo, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 2564. doi:
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      M.–J. Son, C.–K. Joo; The Regulation of NADPH Oxidase by TGF–ß in Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2564.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : TGF–ß responses in epithelial cells are actin rearrangement, ECM accumulation, the generation of reactive oxygen species (ROS), migration, cell arrest, and apoptosis. Among them, ROS production could mediate additional signals associated with the formation of anterior polar or age–related cataract. Therefore, we examined the mechanism of ROS generation by TGF–ß1, especially the regulation of NADPH oxidase activity, known to be a major enzyme of ROS generation

Methods: : We firstly examined if TGF–ß1 could induce ROS generation in epithelial cells, using confocal microscopy which detected fluorescent 2',7'–dichlorofluorescein formed from 2',7'–dichlorofluorescein diacetate and assay of NADPH oxidase activity. To deeply examine the regulation of NADPH oxidase by TGF–ß1, we performed Northern blot analysis for expressions of components of NADPH oxidase complex and determined which of signals could be involved in regulation of their components using specific inhibitors or dominant negative constructs, such as SU6656 (Src inhibition), cycloheximide (the inhibition of de novo protein synthesis) and Smad2/3 DN plasmids

Results: : TGF–ß1 rapidly and transiently induced ROS generation and NADPH oxidase activity in epithelial cells, which were strongly inhibited by SU6656 and cycloheximide, implying that TGF–ß–induced ROS generation would require Src signaling and de novo protein synthesis. In addition, the expression of p67phox, a component of NADPH oxidase, was induced by TGF–ß1, mediated by Smad signaling. Interestingly, TGF–ß–induced ROS generation was dependent on E–cadherin expression; in E–cadherin–expressed MDA–MB–231 cells, ROS generation was induced by TGF–ß1 but not in E–cadherin–deficient cells

Conclusions: : ROS generation induced by TGF–ß is directly mediated by NADPH oxidase, which is depending on Src signaling and de novo protein synthesis such as p67phox, and is dependent on E–cadherin expression. Herein, we suggest a novel mechanism of ROS generation induced by TGF–ß

Keywords: cataract 

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