TGF-ß1 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-ß1 (TGF-ß1) is known to accelerate tissue repair by promoting the synthesis and deposition of extracellular matrix proteins. However, persistence or overactivity of TGF-ß1 during the remodeling phase can potentially lead to fibrosis. The primary objective of this study was, therefore, to determine the effects of TGF-ß1 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-ß1 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-ß1 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 a–smooth muscle actin was markedly reduced in the wounds treated with LAP but was slightly increased in the wounds treated with TGF-ß1. Both neodermis and newly-formed epidermis exhibited a higher degree of maturation in the LAP-treated wounds as compared to TGF-ß1 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.Iran J Med Sci 2006; 31(2): 65-69.