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积雪草苷抑制瘢痕疙瘩成纤维细胞的迁移:涉及 p38 激酶和 PI3K 信号通路。

Madecassoside suppresses migration of fibroblasts from keloids: involvement of p38 kinase and PI3K signaling pathways.

机构信息

Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

出版信息

Burns. 2012 Aug;38(5):677-84. doi: 10.1016/j.burns.2011.12.017. Epub 2012 Feb 22.

DOI:10.1016/j.burns.2011.12.017
PMID:22360962
Abstract

Keloid is a specific skin scar that expands beyond the boundaries of the original injury as it heals. The invasive nature of keloid and notable migratory activity of fibroblasts are a hallmark, which distinguishes keloids from other common scars. Madecassoside, a triterpenoid saponin occurring in Centella asiatica herbs, possesses unique pharmacological properties to enhance wound-healing and diminish keloid formation. However, the effects of madecassoside on the formation of keloid scars have been poorly understood. Here, we focused on the potential of madecassoside on the migration of keloid-derived fibroblasts (KFs) and its mechanism. Primary KF, originating from human earlobe keloids, were purified and cultured, and then treated with madecassoside (10, 30, and 100μM). In both transwell migration assays and scratch-wound-closure assays, KF migration was considerably suppressed by madecassoside pretreatment. Furthermore, KFs treated with madecassoside showed decreased F-actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. By Western blot analysis, madecassoside was shown to remarkably attenuate the phosphorylation of cofilin, p38 MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT signaling, but only exhibited a minor effect on MMP-13 and little effect on ERK1/2 phosphorylation. It was concluded that madecassoside could be of great use in the treatment and/or prevention of hypertrophic scars and keloids.

摘要

瘢痕疙瘩是一种特殊的皮肤瘢痕,在愈合过程中会超出原始损伤的边界扩张。瘢痕疙瘩的侵袭性和明显的成纤维细胞迁移活性是其特征,将其与其他常见瘢痕区分开来。积雪草苷是一种存在于积雪草中的三萜皂苷,具有独特的药理学特性,可以促进伤口愈合和减少瘢痕疙瘩形成。然而,积雪草苷对瘢痕疙瘩形成的影响尚未得到充分理解。在这里,我们专注于积雪草苷对瘢痕疙瘩衍生成纤维细胞(KFs)迁移的潜在作用及其机制。从人耳垂瘢痕疙瘩中分离并培养原代 KF,然后用积雪草苷(10、30 和 100μM)处理。在 Transwell 迁移实验和划痕愈合实验中,积雪草苷预处理可显著抑制 KF 的迁移。此外,用积雪草苷处理的 KFs 显示出 F-肌动蛋白丝减少,这通过异硫氰酸荧光素(FITC)-鬼笔环肽染色和共聚焦显微镜观察得到证实。通过 Western blot 分析表明,积雪草苷可显著减弱丝切蛋白、p38 MAPK 和磷脂酰肌醇-3-激酶(PI3K)/AKT 信号的磷酸化,但对 MMP-13 的作用较小,对 ERK1/2 磷酸化的作用较小。综上所述,积雪草苷可用于治疗和/或预防增生性瘢痕和瘢痕疙瘩。

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