期刊
PHARMACEUTICS
卷 15, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics15020329
关键词
glaucoma surgery; fibrosis; kitasamycin; novel pharmaceutical concepts; specific antifibrotic agent
This study evaluated the antifibrotic potential of kitasamycin (KM) in a TGF-beta 1-mediated fibroblast model. The results showed that KM could inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of proteins involved in fibrosis, suggesting its potential as a specific prevention agent for fibrosis in the future.
One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TGF)-beta 1-mediated fibroblast model was evaluated in vitro. Primary ocular fibroblasts were isolated, cultivated and a dose-response test including determination of the half maximal effective concentration (EC50) for KM was conducted. Transformation of fibroblasts into myofibroblasts was induced by TGF-beta 1and immunofluorescence (IF), and Western blot (WB) analyses were performed with fibroblasts and myofibroblasts. IF analyses were carried out using antibodies against alpha-smooth muscle actin (alpha-SMA) and fibronectin, and protein detection of intracellular and extracellular proteins was performed by WB. Using the dose-response test, the viability, cytotoxicity and EC50 of KM after 24 and 48 h were determined. Fibroblasts exposed to various KM concentrations showed no increase in alpha-SMA and extracellular matrix expression. In TGF-ss1-stimulated myofibroblasts, KM inhibited the expression of alpha-SMA and fibronectin in a concentration-dependent manner. These findings demonstrate that KM could impair the transformation of fibroblasts into myofibroblasts and the expression of proteins involved in fibrotic processes, representing a potential agent for specific fibrosis prevention in future therapeutic concepts.
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