EB research team from the USA identifies a possible target for reducing fibrosis in RDEB skin
New scientific publication with EB House contribution
People with recessive dystrophic epidermolysis bullosa (RDEB) suffer from severe blistering of the skin caused by the lack of a protein called collagen 7 which is essential for proper skin integrity. Further complications in patients involve aberrant wound healing and scarring, as well as fibrosis of the skin. Fibrosis is characterized by the thickening and scarring of connective tissues, which can result in the development of an aggressive form of skin cancer. This process can be induced via different mechanisms, like the activation of the protein Transforming Growth Factor-beta (TGF-ß). The activation of TGF-ß is in turn enhanced by another protein called Thrombospondin-1 (TSP1). Previous investigations have already revealed that RDEB skin cells produce more of TSP1 than skin cells from healthy individuals. Therefore, an EB research group in Philadelphia (USA) together with international collaboration partners studied the role of TSP1 in TGF-ß activation particularly in RDEB skin cells. Their findings were recently published in the Journal of Investigative Dermatology.
They observed that collagen 7 protein attaches to TSP1 in skin cells from healthy individuals, which prevents TSP1 from activating TGF-ß and thus decreasing fibrosis. However, because collagen 7 is lacking in RDEB cells, TSP1 can bind and activate TGF-ß which induces fibrosis. This finding highlights new treatment options for EB patients. Blocking TSP1 could suppress activation of TGF-ß, thereby preventing fibrosis.
In order to test this hypothesis, the scientists developed a tissue model that mimics RDEB skin allowing to test substances that block TSP1. While this approach will not provide a causal therapy, it has the potential to ameliorate or even prevent fibrosis and further complications such as cancer formation. In addition, targeting TSP1 might be a safer approach for RDEB patients, since general blocking of TGF-ß production is associated with severe side effects.
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