The Scar‐in‐a‐Jar: studying potential antifibrotic compounds from the epigenetic to extracellular level in a single well

摘要: Background and purpose:  Fibrosis, a pathological accumulation of collagen in tissues, represents major global disease burden. Effective characterization potential antifibrotic drugs has been constrained by poor formation the extracellular matrix vitro, due to tardy procollagen processing C-proteinase/BMP-1, difficulties relating this cell numbers experimental samples. Experimental approach:  The Scar-in-a-Jar model provided, complete biosynthetic cascade including conversion its subsequent deposition lysyl oxidase-mediated cross-linking, achieved applying biophysical principle macromolecular ‘crowding’. Collagen deposition, velocity morphology can be controlled using negatively charged ‘crowders’ rapid (2 days) mode or mixture neutral an accelerated (6 mode. Combined with quantitative optical bioimaging, novel system allows for situ assessment area deposited collagen(s) per cell. Key results:  Optical evaluation known compounds effective at epigenetic, post-transcriptional/translational/secretional level correlated excellently corresponding biochemical analyses. Focusing on quantitation collagen, was most assessing inhibitors that may have multiple targets, such as microRNA29c, found promising agent. Conclusions implications:  This screening supersedes current vitro fibroplasia models, fast, non-destructive technique. method distinguishes reduction I excluding full C-proteinase/BMP-1 other metalloproteinases.