miR – 155可作为治疗硬皮病的靶点

作者：Qingran Yan1 et al 翻译：熊丽桂

摘要：硬皮病是一种难治性自身免疫性皮肤纤维化疾病。对病损皮肤进行小分子核糖核酸的改变，可能是治疗这种疾病的新方法。我们发现，无论是在系统性硬化症患者还是局限性硬化症患者，或者是与皮肤纤维化相关的区域，都发现miR-155上调。后来，我们证明了miR-155能够作为临床前期的系统性硬化症的潜在治疗靶点。miR-155?/?老鼠能够抑制博来霉素导致的皮肤纤维化。我们甚至发现，局部使用miR-155拮抗剂可以有效治疗小鼠皮下注射博来霉素所致的皮肤纤维化。miR-155的转录停止，具有抑制胶原蛋白合成功能的作用，并且具有同时抑制Wnt/ β-连环蛋白和 Akt两个纤维化前期信号通路的作用。结合以前的报道，我们进一步发现，mir-155是通过直接针对CK1 α和SHIP-1来调节Wnt/ β-连环蛋白和Akt两条通路的。对皮下注射博来霉素的小鼠敲除miR-155基因或在皮肤局部使用miR-155拮抗剂，可以明显抑制皮肤的Wnt/β-catenin和Akt两个信号。总之，我们的资料显示，miR-155蛋白的休止治疗对真皮纤维化确切有效，尤其皮肤局部使用时。

附原文：Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155?/? mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/ β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1 α (CK1 α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.

引自：Qingran Yan,，Jie Chen，Wei L，et al. Targeting miR-155 to Treat .Experimental Scleroderma,Scientific Repo R ts . 6:20314.DOI: 10.1038/srep20314