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Cell biology and faulty brakes in Dupuytren’s

TGF-beta is a protein which lets some cells boss other cells around. It’s manufactured and released by some cells, and other cells change what they are doing when they notice that TGF-beta is around. TGF-beta does different things to different cells, always in a domino effect. For example, fibroblasts respond to TGF-beta by accumulating the protein beta-catenin inside the cells, which then triggers another protein, TCF/LEF, inside the cell nucleus to turn on certain genes which then change what that cell does and looks like. See? Dominos. This study reveals an automatic braking system: Normally, TGF-beta triggers fibroblasts to make collagen, and then that collagen steps on the brakes by blocking TGF-beta. This study suggests how this braking system may be broken in Dupuytren’s: Not only are Dupuytren’s fibroblasts more sensitive to TGF-beta than regular fibroblasts, but Dupuytren fibroblasts manufacture a different mix of collagen (type 1 and type 3) than normal fibroblasts (only type 1), which may not have the same regulatory effect. More studies are in the works – very exciting!