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Full-Text Articles in Ophthalmology
Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan
Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan
Ophthalmology and Visual Science Faculty Publications
Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G₀/G₁ cell cycle inhibition (IC₅₀ 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked …