mirna在硬皮病发病机制中的作用及其在诊断和治疗中的靶向作用

M. Jinnin
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引用次数: 0

摘要

硬皮病是一种以皮肤和内脏组织纤维化为特征的自身免疫性疾病。了解其发病机制和开发新的诊断工具或有效的治疗方法迫在眉睫。长度为19-25个核苷酸的miRNAs,直接结合到靶mrna的3′非翻译区(3′UTRs)的互补序列上,从而调控基因表达。miR-29、-206、-125b、-21、-145、-196、-150、-129-5p、-92a和let-7g等多种mirna可能通过调节胶原、整合素或基质金属蛋白酶的表达与硬皮病纤维化相关。此外,血清miR-29a、-196a、-150、-92a和-142-3p水平与本病的诊断或疾病活动性相关。另一方面,miRNA治疗可能成为治疗多种人类疾病的一种有前景的治疗策略。全身给药let-7减毒博莱霉素诱导小鼠皮肤纤维化,提示抗纤维化效果。
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Contribution of miRNAs to the pathogenesis of scleroderma and targeting them for the diagnosis and treatment
Scleroderma is one of the autoimmune diseases characterized by tissue fibrosis of the skin and internal organs. The understanding of its pathogenesis and the development of new diagnostic tools or effective therapeutic approaches are urgent.miRNAs 19–25 nucleotides in length, directly bind to complementary sequences in the three prime untranslated regions (3´ UTRs) of target mRNAs, leading to the modulation of gene expression. Various miRNAs including miR-29, -206, -125b, -21, -145, -196, -150, -129-5p, -92a, and let-7g may be associated with the fibrosis in scleroderma via regulating the expression of collagens, integrins or matrix metalloproteinases. In addition, serum levels of miR-29a, -196a, -150, -92a, and -142-3p are correlated with the diagnosis or disease activity of this disease. On the other hand, miRNA treatment may become a promising therapeutic strategy in various human diseases. Systemic administration of let-7-attenuated bleomycin-induced mice skin fibrosis, suggesting an antifibrotic effe...
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