Shah M, Foreman D M, Ferguson M W
Department of Cell and Structural Biology, School of Biological Sciences, University of Manchester, UK.
J Cell Sci. 1994 May;107 ( Pt 5):1137-57. doi: 10.1242/jcs.107.5.1137.
Scarring is a major cause of many clinical problems. Scar tissue interferes with growth, impairs function and is aesthetically unpleasant. However, scarring does not appear to be a problem of embryonic life. Embryonic wounds heal with a lower inflammatory and angiogenic response and have a different growth factor profile compared to adult wounds. We have used neutralising antibody to transforming growth factor-beta 1,2 (TGF-beta 1,2) to alter the growth factor profile of cutaneous wounds in adult rodents and studied the effect on scar tissue formation. This paper extends our preliminary report that neutralising antibody to TGF-beta reduces cutaneous scarring in adult rodents. To be effective, the neutralising antibody to TGF-beta needs to be administered at the time of wounding or soon thereafter. The antiscarring effects of this neutralising antibody to TGF-beta were dose dependent. Exogenous addition of neutralising antibody to TGF-beta to incisional wounds reduced the inflammatory and angiogenic responses and reduced the extracellular matrix deposition in the early stages of wound healing without reducing the tensile strength of the wounds. Importantly, the architecture of the neodermis of wounds treated with neutralising antibody to TGF-beta resembled more closely that of normal dermis compared to the unmanipulated control wounds, which healed with an abnormal neodermal architecture resulting in obvious scarring. This study suggests a novel therapeutic approach to reducing scarring in post-natal life.
瘢痕形成是许多临床问题的主要原因。瘢痕组织会干扰生长、损害功能，且外观不佳。然而，瘢痕形成似乎并非胚胎期的问题。与成年伤口相比，胚胎伤口愈合时炎症反应和血管生成反应较低，且生长因子谱不同。我们使用转化生长因子-β1,2（TGF-β1,2）的中和抗体来改变成年啮齿动物皮肤伤口的生长因子谱，并研究其对瘢痕组织形成的影响。本文扩展了我们之前的初步报告，即TGF-β中和抗体可减少成年啮齿动物的皮肤瘢痕形成。为了有效，TGF-β中和抗体需要在受伤时或之后不久给药。这种TGF-β中和抗体的抗瘢痕作用具有剂量依赖性。在切口伤口中外源性添加TGF-β中和抗体可减少炎症反应和血管生成反应，并在伤口愈合早期减少细胞外基质沉积，而不会降低伤口的抗张强度。重要的是，与未处理的对照伤口相比，用TGF-β中和抗体处理的伤口的新真皮结构更接近正常真皮，未处理的对照伤口愈合时新真皮结构异常，导致明显瘢痕形成。这项研究提出了一种减少出生后瘢痕形成的新治疗方法。
