Transdermal siRNA-TGFβ1-337 patch for hypertrophic scar treatment
Transdermal siRNA-TGFβ1-337 patch for hypertrophic scar treatment
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DOI：
10.1016/j.matbio.2013.02.004
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发表时间：
2013-06-24
期刊：
影响因子：
6.9
通讯作者：
Ma, Wenli
中科院分区：
文献类型：
--
作者：
Zhao, Rui;Yan, Qitao;Ma, Wenli
增生性瘢痕(HSC)是一种真皮纤维增生性疾病，其特征是愈合皮肤的红斑、肿胀和瘙痒病变。随着对转化生长因子β1在肝星状细胞发生发展过程中作用的认识的加深，通过下调转化生长因子β1的表达来治疗肝星状细胞是可能的。筛选出能有效干扰转化生长因子β1表达的siRNA。结论：siRNA-转化生长因子β1-337能有效下调HSC成纤维细胞转化生长因子β1的表达。观察siRNA-转化生长因子β1-337对HSC成纤维细胞增殖、细胞周期和细胞凋亡的影响。结果表明，它抑制细胞增殖，使细胞停滞于细胞周期的G1期，并诱导HSC成纤维细胞的凋亡。SiRNA-转化生长因子β1-337透皮贴剂是由siRNA-转化生长因子β1-337与压敏性粘附性水凝胶组成的透皮贴剂。在将人HSC移植到裸鼠体内建立的动物模型上，评估了透皮贴剂的治疗效果。经皮小干扰RNA-转化生长因子β1-337贴剂治疗后，转化生长因子β1的表达降低。结果，治疗导致I型胶原下调，排列规则的瘢痕成纤维细胞显著减少，并发生凋亡；瘢痕大小显著减小。因此，我们的发现表明，经皮siRNA-转化生长因子β1-337贴片是一种潜在的治疗增生性瘢痕的方法。(C)2013爱思唯尔B.V.保留所有权利。
Hypertrophic scarring (HSc) is a fibroproliferative disorder of the dermis characterized by erythematous, swollen, and pruritic lesions of healing skin. An increased understanding of the role of TGF beta 1 in the development of HSc provides the potential for treating HSc by down-regulating TGF beta 1 expression. siRNAs that effectively interfered with TGF beta 1 expression were screened. It was concluded that the siRNA-TGF beta 1-337 was able to effectively down-regulate TGF beta 1 expression in HSc fibroblasts. The effects of siRNA-TGF beta 1-337 on cell proliferation, cell cycle, and apoptosis of HSc fibroblasts were investigated. It was shown that it inhibited cell proliferation, arrested cells in the G1 stage of the cell cycle, and induced apoptosis of HSc fibroblasts. The transdermal patch of siRNA-TGF beta 1-337 was a combination of siRNA-TGF beta 1-337 and a pressure-sensitive adhesive hydrogel. The treatment effects of the transdermal patch were assessed in an animal model established by transplanting human HSc to nude mice. Decreased expression of TGF beta 1 was observed with treatment with the transdermal siRNA-TGF beta 1-337 patch. Consequently, the treatment resulted in type I collagen down-regulation and regularly arranged scar fibroblasts being significantly reduced and undergoing apoptosis; the scar size was decreased significantly. Thus, our findings indicate that a transdermal siRNA-TGF beta 1-337 patch is a potential treatment for hypertrophic scars. (c) 2013 Elsevier B.V. All rights reserved.