State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Invest Dermatol. 2013 May;133(5):1351-60. doi: 10.1038/jid.2012.486. Epub 2013 Jan 10.
Hypertrophic scarring is a common disease affecting millions of people around the world, but there are currently no satisfactory drugs to treat the disease. Exaggerated inflammation and mechanical stress have been shown to be two main mechanisms of excessive fibrotic diseases. Here we found that a benzopyran natural product, xiamenmycin, could significantly attenuate hypertrophic scar formation in a mechanical stretch-induced mouse model. The compound suppressed local inflammation by reducing CD4+ lymphocyte and monocyte/macrophage retention in fibrotic foci and blocked fibroblast adhesion with monocytes. Both in vivo and in vitro studies found that the compound inhibited the mechanical stress-induced profibrotic effects by suppressing proliferation, activation, fibroblast contraction, and inactivating FAK, p38, and Rho guanosine triphosphatase signaling. Taken together, the compound could simultaneously suppress both the inflammatory and mechanical stress responses, which are the two pivotal pathological processes in hypertrophic scar formation, thus suggesting that xiamenmycin can serve as a potential agent for treating hypertrophic scar formation and other excessive fibrotic diseases.
增生性瘢痕是一种常见疾病，影响着全球数百万人，但目前尚无治疗该病的满意药物。过度炎症和机械应激已被证明是过度纤维化疾病的两个主要机制。在这里，我们发现苯并吡喃天然产物厦门霉素可显著减轻机械拉伸诱导的小鼠模型中的增生性瘢痕形成。该化合物通过减少纤维化灶中 CD4+淋巴细胞和单核细胞/巨噬细胞的保留来抑制局部炎症，并与单核细胞一起阻断成纤维细胞的黏附。体内和体外研究均发现，该化合物通过抑制增殖、激活、成纤维细胞收缩以及失活 FAK、p38 和 Rho 鸟苷三磷酸酶信号通路，抑制机械应激诱导的致纤维增生作用。综上所述，该化合物可同时抑制增生性瘢痕形成的两个关键病理过程中的炎症和机械应激反应，因此提示厦门霉素可作为治疗增生性瘢痕形成和其他过度纤维化疾病的潜在药物。
