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Feedback Loops in Dupuytren’s

The best hope for finding a medical cure for Dupuytren’s and other fibrotic conditions is through a better understanding of abnormal cell signalling feedback loops regulating fibrosis. Cellular collagen metabolism regulation is not fully understood. Here are a few puzzle pieces. The protein transforming growth factor beta (TGF-ß), among other things, signals myofibroblasts to produce collagen. Plasminogen Activator is a protein which links with a cell receptor and another protein, Integrin αvß2, to activate Plasmin, an enzyme which counterbalances the effects of TGF-ß. Plasminogen Activator Inhibitor-1 (PAI-1) removes these plasmin receptors and integrins from the cell surfaces, and so too much PAI-1 promotes fibrosis. However, nothing is simple; everything is connected: Too little PAI-1 also promotes fibrosis. Why? The margin of this post is too small to include a full proof, so here is the link to the original resaerch report: