Abstract
SIGNIFICANCE: The healing of injuries, such as those caused by ischemia (myocardial infarction, stroke), trauma, surgery, and inflammation, tends to happen through undesirable and harmful scarring. Current options in reducing scar formation are largely limited to local intervention in accessible tissues. RECENT ADVANCES: We have designed a systemically administered, injury-targeted decorin for scar prevention. The delivery of decorin to injured tissues is achieved by fusing recombinant decorin to a 9-amino acid peptide, CARSKNKDC (CAR), which specifically recognizes the vessels in injured tissues and extravasates into the tissue, delivering decorin with it. CRITICAL ISSUES: Decorin is known to prevent tissue fibrosis and promote tissue regeneration. This activity of decorin is based on inhibition of TGF-β and some other regulatory activities. In addition to serving as a delivery vehicle, the CAR component endowed decorin with much stronger neutralizing activity against TGF-β1 in vitro than is obtained with nontargeted decorin. The CAR-decorin fusion protein promoted wound healing in a mouse skin wound model and suppressed scar formation at doses at which nontargeted decorin was inactive. These results show that selective targeting enhances specificity and potency of an antiscarring compound. FUTURE DIRECTIONS: Targeted decorin provides a new, systemic option for the treatment of scarring and fibrotic diseases.