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Reversal of ε(γ-Glutamyl) Lysine Cross-Linking and Down-Regulation of Fibronectin and Tissue Transglutaminase (tTGase) Activity in Hypertrophic Scars Following Treatment with 0.8% 1,4 DAB 2HCL

Authors: Hardas, B.¹; Dolynchuk, K.²; Jacob, C.¹; Griffin, M.³; Panchal, C.¹

Source: Wound Repair and Regeneration, Volume 12, Number 2, April 2004 , pp. A19-A19(1)

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Abstract:

Hypertrophic scar formation is an unfavorable condition which is difficult to predict, prevent or treat. Although much research has been done on understanding hypertrophic scar formation, the exact underlying molecular mechanism has not been fully elucidated.

Hypertrophic scars younger than 6 months are known to over-express tTGase. It has been shown that treatment of hypertrophic scars with topical 1, 4 DAB 2HCl inhibited ε(γ-glutamyl) lysine cross-linking ⁴ .

In the current study, 12 paired scar biopsies, either treated or untreated with 1, 4 DAB 2HCl were examined for the presence of ε(γ-glutamyl) lysine cross-linking by fluorescence immunohistochemistry. In situ tTGase enzyme activity, expression of latent tissue TGF-β binding protein-1 (LTBP-1) and fibronectin were also examined. Scars showed a marked reduction of ε(γ-glutamyl) lysine cross-linking following treatment with 1, 4 DAB 2HCl. Although the treated samples did not show any change in expression of tTGase, its in situ activity was noticeably reduced. Treated samples also demonstrated down-regulation of fibronectin and LTBP-1. Results suggest that topical treatment of hypertrophic scars with 1,4 DAB 2HCl not only reduced ε(γ-glutamyl) lysine cross-linking but also reduced tTGase activity, expression of fibronectin and LTBP-1 ⁵ which are known to play a role in extracellular matrix storage of transforming grown factor-β(TGF-β), responsible for wound healing and scar formation.

⁴Dolynchuk KN. Wound Rep Reg 1996; 4(1): 16-20.

⁵Verderio E, Gaudry C et al. J. Histochem 1999; 47(11): 1417-1432.

Document Type: Abstract

DOI: http://dx.doi.org/10.1111/j.1067-1927.2004.0abstractbn.x

Affiliations: 1: 1Procyon Biopharma Inc., Montreal, QC, CAN 2: 2Dept. of Plastic Surgery, University of Manitoba, Winnipeg, MB, CAN 3: 3Nottingham Trent University, Nottingham, UK

Publication date: 2004-04-01