Adenovirus-relaxin gene therapy for keloids: implication for reversing pathological fibrosis

Abstract

Background Keloids or hypertrophic scars are pathological proliferations of the dermal skin layer resulting from excessive collagen deposition. Because the hormone relaxin (RLX) inhibits collagen synthesis and expression in stimulated fibroblasts, an adenovirus expressing RLX (dE1-RGD/lacZ/RLX) was generated.Objectives To investigate the effect of RLX-expressing adenovirus on expression of various extracellular matrix (ECM) components in primary keloid spheroids.Methods The expression levels of type I and III collagen, fibronectin and elastin were investigated by immunohistochemistry in primary keloid spheroids transduced with the RLX-expressing adenovirus.Results Immunohistochemical analysis showed that expression of major ECM components (e. g. type I and III collagen, elastin and fibronectin) was markedly reduced in primary keloid spheroids transduced with dE1-RGD/lacZ/RLX.Conclusions These results suggest that the antifibrotic effect of RLX-expressing adenovirus may have therapeutic effects on keloids by reversing pathological fibrosis and preventing keloid recurrence after surgical excision.This work was supported by grants from the Ministry of Knowledge Economy (10030051, C-O.Y.), the Korea Science and Engineering Foundation (R15-2004-024-02001-0, 2009K001644, 2010-0029220, C-O.Y.), Korea Food and Drug Administration (KFDA-10172-332, C-O.Y.) and a Faculty Research Grant from Yonsei University College of Medicine (6-2007-0182, W.J.L.). I.K.C. is a graduate student sponsored by KOSEF through the National Core Research Center for Nanomedical Technology, Yonsei University College of Medicine, Seoul, Korea