allele frequency of 0.0002 and is predicted to be a damaging mutation. Recombinant human Lys679Met FXIII-A demonstrated reduced fibrin crosslinking activity in vitro. Of note, treatment of fibroblasts with media containing Lys679Met FXIII-A led to enhanced adhesion, proliferation and type I collagen synthesis. Immunostaining revealed co-localization between FXIII-A and 41 integrins, more prominently for Lys679Met FXIII-A than wild-type. In addition, both the 41 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine- Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may leads to a conformational change in the FXIII-A protein that enhances 4-integrin binding and provide insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma.
|Journal of Investigative Dermatology
|Published - 7 Aug 2019