High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation.
High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation.
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DOI：
10.3390/ijms19010076
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发表时间：
2017-12-28
影响因子：
5.6
通讯作者：
Lee WJ
中科院分区：
文献类型：
--
作者：
Kim J;Park JC;Lee MH;Yang CE;Lee JH;Lee WJ
新出现的研究表明，高迁移率族蛋白1(HMGB1)参与了系统性纤维化疾病，但其在皮肤瘢痕形成过程中的作用尚未被研究。我们推测HMGB1可能促进成纤维细胞活性，导致异常皮肤瘢痕形成。对正常和瘢痕疙瘩成纤维细胞的体外伤口愈合实验表明，HMGB1促进了这两种成纤维细胞的迁移，增加了迁移速度和移动距离。HMGB1抑制剂甘草酸(GA)对这两种活性的抑制作用相反。免疫印迹法检测细胞外信号调节激酶1/2、蛋白激酶B、活化B细胞核因子轻链增强子(NF-κB)的蛋白水平，以探讨其下游机制。与对照组相比，HMGB1可上调ERK1/2、AKT和NF-κB的表达水平，这一作用可被GA抑制。HMGB1促进正常和瘢痕疙瘩成纤维细胞迁移的程度与转化生长因子-β相当。我们的结论是，HMGB1通过晚期糖基化终产物受体-丝裂原活化蛋白激酶和核因子-κB相互作用的信号通路激活成纤维细胞。进一步了解HMGB1与皮肤纤维化的关系可能会导致一种有前途的临床方法来管理异常瘢痕。
Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)—mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.
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发表时间：
2007-12-01
影响因子：
4.9
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