摘要
微RNA(microRNAs,miRNAs)是在基因编码中起负性调控作用的内源性短链非编码RNA(non-coding RNAs,ncRNAs),是生理和病理过程中基因表达必不可少的转录后调控物。miRNAs占人类基因组的1%～2%,通过与各自的mRNA结合并抑制其翻译,调节大于50%的人类基因及60%的哺乳动物蛋白质编码基因。系统性硬化症(systemic sclerosis,SSc)的发病机制由复杂的miRNAs网络调控。这些miRNAs位于与SSc纤维化相关的基因组区域,通过参与调节重要的细胞信号通路,如TGF-β、Wnt/β-catenin、TLR-4、IL和PDGF-β等,在SSc纤维化过程中发挥作用。同时,还与细胞信号转导、基质修复与重塑、成纤维细胞凋亡、胶原蛋白质合成和细胞外基质(extracellular matrix,ECM)沉积等相关。充分了解miRNAs在SSc纤维化中的重要性,有助于为SSc的诊断提供新的生物标记,为治疗提供新策略。本文综述了miRNAs在SSc纤维化过程中参与调节的这些复杂细胞信号通路的作用及机制,以期为SSc诊断、严重程度判断、预后评估,以及寻求潜在治疗靶点提供新思路。
MicroRNAs (miRNAs) are endogenous shortchain noncoding RNAs (ncRNAs) that plays a negative regulatory role in gene coding and is an essential posttranscriptional regulators for gene expression in physiological and pathological processes. MicroRNAs account for 1%-2% of the human genome. miRNAs regulate >50% of human genes through binding to the respective mRNAs and inhibiting their translation and may repress more than 60% of all mammalian protein-coding genes. The pathogenesis of systemic sclerosis (SSc) is regulated by a complex network of miRNAs that are located in the genomic region associated with SSc fibrosis, by participating in the regulation of important cell signaling pathways such as transforming growth factor-β (TGF-β), wnt/β-catenin, toll-like receptors-4 (TLR-4), interleukin (IL) and platelet derived growth factor-β (PDGF-β) in SSc fibrosis. They also participate in cell signaling, repairing and remodeling, fibroblast apoptosis, collagen synthesis, extracellular matrix (ECM) deposition and so on. To fully understand the importance of miRNAs in SSc fibrosis can help in finding potential new biomarkers for the diagnosis of SSc and strategies for treatment. This paper reviews the role and mechanisms of miRNAs in regulating these complex cellular signaling pathways in the process of SSc fibrosis, which may provide further evidences for SSc diagnosis,severity judgment, prognosis assessment, and search for potential therapeutic targets.
作者
王红权
梅振华
詹杰
WANG Hong-Quan;MEI Zhen-Hua;ZHAN Jie(Rheumatology and Immunology Department,Jingmen No.2People's Hospital,Jingmen448000,Hubei,China;Functional Inspection Section,Jingmen No.2People's Hospital,Jingmen448000,Hubei,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2018年第12期1286-1293,共8页
Chinese Journal of Biochemistry and Molecular Biology
关键词
微RNA
系统性硬化症
细胞信号通路
纤维化
成纤维细胞
microRNAs (miRNAs)
systemic sclerosis (SSc)
cell signaling pathway
fibrosis
fibroblasts
