TGF-β1 latency associated peptide promotes remodeling of healing cutaneous wounds in the rat

Background: The process of wound healing involves integrated events including inflammation, granulation tissue formation, matrix deposition and remodeling. Growth factors play a key role in the process. Among them transforming growth factor-β1 (TGF-β1) is known to accelerate tissue repair by promoting the synthesis and deposition of extracellular matrix proteins. However, persistence or overactivity of TGF-β1 during the remodeling phase can potentially lead to fibrosis. The primary objective of this study was, therefore, to determine the effects of TGF-β1 inactivation, by its latency associated peptide (LAP), on the cutaneous healing wounds. Methods: Excisional wounds were generated on the back of male adult rats. Wounds received TGF-β1 or LAP during the post-inflammatory phase. Expression of type I collagen and a-smooth muscle actin was evaluated by Western blotting. Wound maturation was further assessed by histology and immunohistochemical methods using specific antibody for proliferating cell nuclear antigen (PCNA). Results: Wounds treated with TGF-β1 showed a marked increase in the level of type I collagen, whereas no significant changes were observed in the wounds treated with LAP as compared to that in control. Expression of α-smooth muscle actin was markedly reduced in the wounds treated with LAP but was slightly increased in the wounds treated with TGF-β1. Both neodermis and newly-formed epidermis exhibited a higher degree of maturation in the LAP-treated wounds as compared to TGF-β1 treated wounds. Conclusion: Local administration of LAP seems to be beneficial to tissue remodeling. It promotes wound maturation and, may prevent fibrosis and hypertrophic scarring.