April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
RhoA/ROCK Pathway Mediated the Expression of Type1 Collagen Induced by TGF-β2 in Trabecular Meshwork Cells
Author Affiliations & Notes
  • T. Fujimoto
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • M. Inoue-Mochida
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • T. Inoue
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • N. Ohtsu
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • T. Kameda
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
    Ophthalmology and Visual Sciences, Kyoto Univ Grad Sch of Med, Kyoto, Japan
  • N. Kasaoka
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • K. Kimoto
    Ophthalmology, Oita Medical University, Yufu-shi, Japan
  • H. Tanihara
    Ophthalmology and Visual Science, Kumamoto Univ Grad Sch of Med Sci, Kumamoto, Japan
  • Footnotes
    Commercial Relationships  T. Fujimoto, None; M. Inoue-Mochida, None; T. Inoue, None; N. Ohtsu, None; T. Kameda, None; N. Kasaoka, None; K. Kimoto, None; H. Tanihara, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3211. doi:
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      T. Fujimoto, M. Inoue-Mochida, T. Inoue, N. Ohtsu, T. Kameda, N. Kasaoka, K. Kimoto, H. Tanihara; RhoA/ROCK Pathway Mediated the Expression of Type1 Collagen Induced by TGF-β2 in Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3211.

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

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Abstract

Purpose: : Transforming growth factor (TGF)-β2 is reported to cause the increase of intraocular pressure in glaucoma by inducing the accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM). The aim of this study is to examine whether the RhoA/ROCK pathway is involved in TGF-β2-induced collagen expression in a human TM cells (HTM) and porcine TM cells (PTM).

Methods: : The effect of TGF-β2 on RhoA activation was evaluated by pull-down assay. Transcriptional activities of the COL1A2 were evaluated by dual-luciferase reporter assay with the induction of constitutive active RhoA. The effect of selective ROCK inhibitor, Y27632, on type I collagen synthesis induced by TGF-β2 was assessed by ELISA.

Results: : RhoA was activated at 30 min after stimulation with 2.5 ng/ml TGF-β2 in PTM and HTM. Relative RhoA activities were 2.9 and 3.5-fold increased in PTM and HTM respectively. Transcriptional activities of COL1A2 were 1.3-fold increased by TGF-β2 stimulation. Similarly, constitutive active RhoA increased COL1A2 promoter activity. Type 1 collagen in the HTM culture medium was 1.8-fold increased at 48 hours after stimulation with TGF-β2. Combined treatment withTGF-β2 and Y-27632 showed 1.2-fold increase in culture medium when compared with untreated HTM..

Conclusions: : These results suggest that the RhoA/ROCK pathway plays a role in relaying TGF-β2 signal transduction to type I collagen synthesis in TM.

Keywords: trabecular meshwork • extracellular matrix 
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