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白藜芦醇通过靶向 HIF-1α 抑制瘢痕成纤维细胞的增殖并促进其凋亡。

Resveratrol inhibits proliferation and promotes apoptosis of keloid fibroblasts by targeting HIF-1α.

机构信息

Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China.

Department of Ear-Nose-Throat, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Shandong, China.

出版信息

J Plast Surg Hand Surg. 2020 Oct;54(5):290-296. doi: 10.1080/2000656X.2020.1771719. Epub 2020 Jun 4.

Abstract

A keloid is characterized by red, tickling, hard, and irregular raised tissues, and it tends to outgrow its origin. It frequently occurs in young adults and appears to be refractory to prevailing therapies. Resveratrol is a new drug that has anti-proliferative effect. In this study, keloid-derived fibroblasts were cultured under hypoxia environment and was treated by resveratrol. CCK-8 assay and Annexin V-FITC were used to evaluate cell activity and apoptosis level. Western blot and RT-qPCR were also used to assess the expression of HIF-α, Collagen I and Collagen III. Besides, siRNA was also used to explore the mechanisms of resveratrol's effect. In this study, hypoxia promotes proliferation and inhibits apoptosis of keloid fibroblasts. These findings highlight the potential obstacle in treating keloids. Furthermore, we demonstrated that resveratrol could reverse the effect of hypoxia on keloids through down-regulation of HIF-1α. Moreover, collagen synthesis in keloid fibroblasts was also inhibited by resveratrol, which corresponded with HIF-1α suppression. These results provide evidence for resveratrol's treatment effect against keloids through inhibiting cell proliferation and promoting cell apoptosis, while, HIF-1α may play the key role in this process.

摘要

瘢痕疙瘩的特征为红色、瘙痒、坚硬和不规则的凸起组织,且其有过度生长的趋势。它常发生于年轻人,似乎对现有疗法具有抗性。白藜芦醇是一种具有抗增殖作用的新药。在这项研究中,将瘢痕疙瘩衍生的成纤维细胞在低氧环境下培养,并使用白藜芦醇进行处理。CCK-8 检测和 Annexin V-FITC 用于评估细胞活性和凋亡水平。Western blot 和 RT-qPCR 也用于评估 HIF-α、Collagen I 和 Collagen III 的表达。此外,还使用 siRNA 来探讨白藜芦醇作用的机制。在这项研究中,低氧促进了瘢痕疙瘩成纤维细胞的增殖并抑制了其凋亡。这些发现凸显了治疗瘢痕疙瘩的潜在障碍。此外,我们证明白藜芦醇通过下调 HIF-1α 可以逆转低氧对瘢痕疙瘩的作用。此外,白藜芦醇还抑制了瘢痕疙瘩成纤维细胞中的胶原合成,这与 HIF-1α 的抑制作用相对应。这些结果为通过抑制细胞增殖和促进细胞凋亡来治疗瘢痕疙瘩提供了证据,而 HIF-1α 可能在这个过程中发挥关键作用。

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