Gene delivery of a mutant TGF?3 reduces markers of scar tissue formation after cutaneous wounding.

ABSTRACT: The transforming growth factor-? (TGF?) family plays a critical regulatory role in repair and coordination of remodeling after cutaneous wounding. TGF?1-mediated chemotaxis promotes the recruitment of fibroblasts to the wound site and their resultant myofibroblastic transdifferentiation that is responsible for elastic fiber deposition and wound closure. TGF?3 has been implicated in an antagonistic role regulating overt wound closure and promoting ordered dermal remodeling. We generated a mutant form of TGF?3 (mutTGF?3) by ablating its binding site for the latency-associated TGF? binding protein (LTBP-1) in order to improve bioavailability and activity. The mutated cytokine is secreted as the stable latency-associated peptide (LAP)-associated form and is activated by normal intracellular and extracellular mechanisms including integrin-mediated activation but is not sequestered. We show localized intradermal transduction using a lentiviral vector expressing the mutTGF?3 in a mouse skin wounding model reduced re-epithelialization density and fibroblast/myofibroblast transdifferentiation within the wound area, both indicative of reduced scar tissue formation.

SUBMITTER: Waddington SN 

PROVIDER: S-EPMC2997585 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature