首页> 中文期刊> 《国际口腔医学杂志》 >重组人转化生长因子β3在瘢痕预防中的作用

重组人转化生长因子β3在瘢痕预防中的作用

         

摘要

Recombinant human transforming growth factor(TGF)β3 is an important cytokine for formation of healthy skin and healing response of embryos without scarring. In actively growing hypertrophic scar fibroblasts, the expression of TGFβ2 increases and TGFβ3 is low. However, in embryonic scar-free healing, TGFβ3 is high. When TGFβ1, TGFβ2, and TGFβ3 combine with the same receptor complex on the cell surface, TGFβ3 induces the receptor to compete with TGFβ1 and TGFβ2 to reduce their expression and inhibit the formation of scars. In the late period of wound healing, TGFβ3 reduces scar size to reverse the effects of TGFβ1 and TGFβ2 by decreasing the aggregates of inflammatory cells and the deposition of connective tissue, ensuring wound healing and preventing excessive scarring. Preclinical safety and toxicology studies suggest that the TGF β family of proteins accumulate mainly in the liver(~60%) and in other tissues, including the kidneys(~20%) and the blood(~10%). In addition, the TGFβfamily of proteins minimally(<10%) accumulates in the lungs, spleen, adrenals, stomach, small intestine, cardiac and skeletal muscles, and cerebral cortex. Safety pharmacology studies investigating i.v. dosing of recombinant human TGFβ3 in rats and dogs have demonstrated the absence of adverse effects on major systems, including the central nervous system and respiratory or cardiovascular functions at doses up to and including 3μg·kg-1 following prolonged(daily for 3 months) administration. Recombinant human TGFβ3 was injected into the skin in the cut edge of adult rats to reduce distinct scars and to improve skin construct.%重组人转化生长因子(TGF)β3是一种健康皮肤形成和胚胎无瘢痕愈合反应的重要的细胞因子。在生长较活跃的增生性瘢痕成纤维细胞中,TGFβ2表达增加,TGFβ3表达较低;而在胚胎期皮肤无瘢痕愈合时,TGFβ3的表达水平较高。TGFβ1、TGFβ2和TGFβ3与同一个细胞表面受体复合体结合,TGFβ3则通过与TGFβ1和TGFβ2竞争受体,下调二者的表达,从而抑制瘢痕的形成。在伤口愈合后期,TGFβ3通过减少炎症细胞聚集和结缔组织沉积减少瘢痕拮抗TGFβ1和TGFβ2的作用,既能保证伤口的愈合,又不致瘢痕过度。临床前安全性和毒理学研究显示,TGFβ家族60%沉积于肝脏、20%沉积于肾脏,大于10%沉积于血液系统,小于10%沉积于肺、脾、肾上腺、胃、小肠、心脏、骨骼肌和大脑皮质。安全药理学研究显示,老鼠和犬体内持续3个月维持3μg每千克体质量的重组人TGFβ3不会对其中枢神经系统、呼吸系统和心血管系统产生不利影响。在成年鼠皮肤创缘皮内注射重组人TGFβ3,可明显减少创缘瘢痕和改善其皮肤结构。

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