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- Title
Silibinin inhibits myofibroblast transdifferentiation in human tenon fibroblasts and reduces fibrosis in a rabbit trabeculectomy model.
- Authors
Chen, Yi‐Hao; Liang, Chang‐Min; Chen, Ching‐Long; Chen, Jiann‐Torng; Chang, Yun‐Hsiang; Lu, Da‐Wen; Chien, Ke‐Hung; Tai, Ming‐Cheng
- Abstract
. Purpose: To investigate the effect of silibinin in myofibroblast transdifferentiation and in animal trabeculectomy models. Methods: The effect of silibinin on the expression of α-smooth muscle actin (α-SMA) and vimentin in response to transforming growth factor-β1 (TGF-β1) was determined in human tenon fibroblasts (HTFs). Cell migration and collagen contraction arrays were used to demonstrate the functionality of silibinin-modulated HTFs. ELISA analysis was used to determine the effect of silibinin on the release of type 1 collagen and connective tissue growth factor (CTGF). The effect of silibinin on the activation of the TGF-β receptor-related pathway was evaluated by Western blotting. A rabbit model of trabeculectomy was established to assess the effect of silibinin in vivo. Results: TGF-β1 elevated the expression of α-SMA and vimentin in HTFs; this elevation was inhibited by silibinin. TGF-β1 increased cell migration and collagen contraction of HTFs, which were also suppressed by silibinin. The production of both CTGF and type 1 collagen in TGF-β1-treated HTFs was inhibited by silibinin. The effects of silibinin on TGF-β1-stimulated HTFs were mediated via the down-regulation of TGF-β receptor-related SMAD signalling pathways. In the rabbit model of trabeculectomy, silibinin increased the period of decreasing intraocular pressure after trabeculectomy and reduced the production of collagen and α-SMA at the site of blebs in vivo. Conclusion: Silibinin inhibited the TGF-β receptor-related signalling pathway in TGF-β-treated HTFs and several of the downstream events associated with myofibroblast transdifferentiation. Silibinin also improved the outcome of trabeculectomies by reducing the fibrotic response in the bleb tissue in vivo.
- Subjects
SILIBININ; MYOFIBROBLASTS; FIBROBLASTS; ACTIN; CELL migration; CONNECTIVE tissue growth factor; WESTERN immunoblotting; INTRAOCULAR pressure
- Publication
Acta Ophthalmologica (1755375X), 2013, Vol 91, Issue 7, pe506
- ISSN
1755-375X
- Publication type
Article
- DOI
10.1111/aos.12160