| First Author | Cianfarani F | Year | 2019 |
| Journal | Matrix Biol | Volume | 81 |
| Pages | 3-16 | PubMed ID | 30528862 |
| Mgi Jnum | J:282253 | Mgi Id | MGI:6378230 |
| Doi | 10.1016/j.matbio.2018.12.001 | Citation | Cianfarani F, et al. (2019) Decorin counteracts disease progression in mice with recessive dystrophic epidermolysis bullosa. Matrix Biol 81:3-16 |
| abstractText | Loss-of-function mutations in the gene encoding type VII collagen underlie recessive dystrophic epidermolysis bullosa (RDEB), a disease characterized by skin and mucosal blistering, impaired wound healing, and diffuse dermal inflammation and fibrosis. Transforming growth factor-beta signaling plays a crucial role in determining RDEB fibrotic microenvironment that leads to the development of disabling secondary disease manifestations, including hand and foot deformities. Experimental findings indicate that expression levels of decorin, a small leucine-rich proteoglycan and an endogenous TGF-beta inhibitor, can modulate RDEB disease phenotype by contrasting dermal fibroblast fibrotic behavior. In this study, the ability of decorin to modify RDEB course was investigated by systemically treating RDEB mice with a lentivirus expressing human decorin. Overexpressed decorin was able to enhance survival, and to limit digit contraction and the development of paw deformities. These effects were associated with decreased TGF-beta1 levels and TGF-beta signaling activation. Fibrotic traits were strongly reduced in paw skin and also attenuated in the non-chronically injured back skin. However, the expression of pro-inflammatory proteins was not decreased in both paw and back skin. Our findings confirm TGF-beta role in promoting fibrosis and disease progression in RDEB, and show that decorin counteracts disease manifestations by inhibiting TGF-beta activation. More generally, our data indicate that modifying extracellular matrix composition is an option to improve RDEB disease course. |
