Sisco Mark, Kryger Zol B, O'Shaughnessy Kristina D, Kim Peter S, Schultz Greg S, Ding Xian-Zhong, Roy Nakshatra K, Dean Nicholas M, Mustoe Thomas A
Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, 675 N. St. Clair, Chicago, IL 60611, USA.
Wound Repair Regen. 2008 Sep-Oct;16(5):661-73. doi: 10.1111/j.1524-475X.2008.00416.x.
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-beta 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.
在愈合伤口和多种纤维化疾病中均观察到结缔组织生长因子（CTGF/CCN2）表达增强。它似乎能增强转化生长因子-β的多种作用，并且已被证明具有独立的促纤维化功能。尽管有这些观察结果，但其对皮肤伤口愈合以及从伤口到瘢痕转变的重要性仍未明确界定。在本研究中，我们使用已建立的兔模型来评估CTGF在皮肤伤口愈合和增生性瘢痕形成中的作用。我们发现CTGF mRNA在增生性瘢痕中持续上调。用针对CTGF的反义寡核苷酸处理伤口对早期伤口闭合没有可测量的影响。然而，反义疗法显著限制了随后的增生性瘢痕形成。CTGF的抑制与瘢痕中肌成纤维细胞数量的显著减少以及TIMP-1、I型和III型胶原转录的降低有关。这些发现证实CTGF是该模型中增生性瘢痕形成的关键介质。它在此环境中对肌成纤维细胞的作用提示了其发挥这一作用的机制。它在早期愈合中的有限参与意味着它可能是损伤后调节增生性瘢痕形成的一个有用且特异性的靶点。
