Decorin counteracts disease progression in mice with recessive dystrophic epidermolysis bullosa

Matrix Biol. 2019 Aug:81:3-16. doi: 10.1016/j.matbio.2018.12.001. Epub 2018 Dec 5.


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-β 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-β 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-β1 levels and TGF-β 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-β role in promoting fibrosis and disease progression in RDEB, and show that decorin counteracts disease manifestations by inhibiting TGF-β activation. More generally, our data indicate that modifying extracellular matrix composition is an option to improve RDEB disease course.

Keywords: Disease modifying therapy; Extracellular matrix; Fibrosis; Genodermatoses; Inflammation; Skin repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Decorin / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Epidermolysis Bullosa Dystrophica / genetics
  • Epidermolysis Bullosa Dystrophica / metabolism
  • Epidermolysis Bullosa Dystrophica / therapy*
  • Genetic Vectors / administration & dosage*
  • Humans
  • Lentivirus / genetics
  • Mice
  • Signal Transduction
  • Survival Analysis
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Treatment Outcome


  • DCN protein, human
  • Decorin
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1