September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Cytosporone B inhibits the TGF-β–induced expression of a–smooth muscle actin and contractility in human corneal fibroblasts.
Author Affiliations & Notes
  • Naoyuki Morishige
    Ophthalmology, Yamaguchi Univ Grad Sch of Med, Ube, Yamaguchi, Japan
  • Yukiko Morita
    Ophthalmology, Yamaguchi Univ Grad Sch of Med, Ube, Yamaguchi, Japan
  • Shizuka Murata
    Ophthalmology, Yamaguchi Univ Grad Sch of Med, Ube, Yamaguchi, Japan
  • Footnotes
    Commercial Relationships   Naoyuki Morishige, None; Yukiko Morita, None; Shizuka Murata, None
  • Footnotes
    Support  JSPS KAKENHI grant number 15K20264
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2363. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Naoyuki Morishige, Yukiko Morita, Shizuka Murata; Cytosporone B inhibits the TGF-β–induced expression of a–smooth muscle actin and contractility in human corneal fibroblasts.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2363.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Cytosporone B (CsnB) is an antagonist for the nuclear receptor transcription factor NR4A1, known as Nur77, which contributes to the regulation of apoptosis and glucose homeostasis. Recently, it is reported that NR4A1 is related to tissue scarring by regulating transforming growth factor–b (TGF-β) signaling. To investigate the role of NR4A1 in human corneal fibroblasts (HCFs), we examined the effects of CsnB on the expression of a–smooth muscle actin (α-SMA) and contractility in these cells induced by stimulation with TGF-β.

Methods : Cultured HCFs were stimulated with TGF-β (10 ng/ml) in the presence of various concentrations (0 to 10 μM) of CsnB for 3 days, after which the cells were lysed and subjected to immunoblot analysis with antibodies to α-SMA. HCFs were also cultured in collagen gels and exposed to CsnB (1 μM), TGF-β (10 ng/ml), or neither or both agents for 3 days, after which the change in gel diameter was determined as a measure of cell contractility.

Results : The TGF-β–induced expression of α-SMA in HCFs was inhibited by CsnB in a concentration-dependent manner. The diameter of HCF-containing collagen gels after culture for 3 days was 7.8 ± 0.8, 8.3 ± 0.3, 7.0 ± 0.3, or 8.0 ± 0.9 mm in the absence of additions or in the presence of CsnB, TGF-β, or both agents, respectively.

Conclusions : CsnB inhibited TGF-β–induced contraction of HCFs, likely as a result of its attenuation of the up-regulation of α-SMA expression. Our results suggest that NR4A1 mediates these effects of TGF-β in HCFs, and that CsnB warrants further investigation as a potential therapeutic modulator of corneal stromal contraction and scarring.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×