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