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Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo
Author(s) -
Sisco Mark,
Kryger Zol B.,
O'Shaughnessy Kristina D.,
Kim Peter S.,
Schultz Greg S.,
Ding XianZhong,
Roy Nakshatra K.,
Dean Nicholas M.,
Mustoe Thomas A.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2008.00416.x
Subject(s) - ctgf , wound healing , connective tissue , scars , growth factor , hypertrophic scar , myofibroblast , fibrosis , medicine , pathology , cancer research , immunology , receptor
Augmented expression of connective tissue growth factor (CTGF/CCN2) is observed in healing wounds and in a variety of fibrotic disorders. It appears to enhance many of the effects of transforming growth factor‐β and has been shown to have independent fibrogenic functions. Despite these observations, its importance to dermal wound healing and the transition from wound to scar remains poorly defined. In this study, we use established rabbit models to evaluate the roles of CTGF in dermal wound healing and hypertrophic scarring. We show that CTGF mRNA demonstrates persistent up‐regulation in hypertrophic scars. Treatment of wounds with antisense oligonucleotides to CTGF has no measurable effect on early wound closure. However, antisense therapy significantly limits subsequent hypertrophic scarring. Inhibition of CTGF is associated with a marked reduction in the number of myofibroblasts in scars and decreased transcription of TIMP‐1 and types I and III collagen. These findings confirm CTGF to be a key mediator of hypertrophic scarring in this model. Its effect on myofibroblasts in this setting suggests a mechanism whereby it plays this role. Its limited participation in early healing implies that it may be a useful and specific target for modulating hypertrophic scarring following injury.