May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Suppression of Transforming Growth Factor-β Effects in Rabbit Subconjunctival Fibroblasts by Activin Receptor-Like Kinase Inhibitors
Author Affiliations & Notes
  • J. Sapitro
    Department of Ophthalmology, Summa Health System, Akron, Ohio
  • A. Krishnan
    Department of Ophthalmology, Summa Health System, Akron, Ohio
  • X. Qiu
    Department of Medicinal Chemistry and Pharmacognosy,
    University of Illinois at Chicago, Chicago, Illinois
  • B. Y. J. T. Yue
    Department of Ophthalmology and Visual Sciences,
    University of Illinois at Chicago, Chicago, Illinois
  • H. Nakamura
    Department of Ophthalmology, Summa Health System, Akron, Ohio
  • Footnotes
    Commercial Relationships  J. Sapitro, None; A. Krishnan, None; X. Qiu, None; B.Y.J.T. Yue, None; H. Nakamura, None.
  • Footnotes
    Support  American Health Assistance Foundation G2006-014 and National Eye Institute core grant EY01792
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4154. doi:https://doi.org/
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    • Get Citation

      J. Sapitro, A. Krishnan, X. Qiu, B. Y. J. T. Yue, H. Nakamura; Suppression of Transforming Growth Factor-β Effects in Rabbit Subconjunctival Fibroblasts by Activin Receptor-Like Kinase Inhibitors. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4154. doi: https://doi.org/.

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

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Abstract

Purpose: : To evaluate the efficacy of activin receptor-like kinase (ALK) inhibitors in blocking the transforming growth factor-β (TGF-β) pathway in cultured rabbit subconjunctival fibroblasts. TGF-β2 is a cytokine involved in directing wound-healing responses in the eye including scarring following glaucoma filtration surgery.

Methods: : Subconjunctival fibroblasts derived from New Zealand white rabbits were incubated with or without 2 ng/mL of TGF-β2 and treated with various concentrations of selected ALK inhibitors, SB-431542 and A-83-01, for 48 and 72 hours. The expression of connective tissue growth factor (CTGF), a TGF-β downstream mediator, was evaluated by Western blotting. Two other proteins known to be induced by TGF-β treatment, α-smooth muscle actin (α-SMA) and fibronectin, were also examined. In addition, the cell morphology of the fibroblasts was assessed microscopically.

Results: : The CTGF expression was found to be suppressed in TGF-β2-treated cultures at both 48 and 72 hour time points by 3 nM SB-431542 and 1 nM A-83-01. The suppressive effects were more pronounced when the inhibitor concentrations were increased to 10 and 3 nM, respectively. A similar reduction of α-SMA and fibronectin levels was also observed at all concentrations of the inhibitors tested. TGF-β2 caused the fibroblasts to assume an even more elongated morphology. The TGF-β2-induced morphological change could be averted by treatment of either 10 nM of SB-431542 or 3 nM of A-83-01.

Conclusions: : Both SB-431542 and A-83-01 are effective in inhibiting the signaling pathway of TGFβ in rabbit subconjunctival fibroblasts. A-83-01 appears to be at least 3 fold more effective than SB-431542. These inhibitors may be useful in the suppression of ocular scarring, such as that seen in glaucoma filtration surgery.

Keywords: wound healing • growth factors/growth factor receptors 
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