摘要
背景:非编码RNA随着高通量技术的发展而逐渐引发关注,其广泛参与呼吸系统各疾病病程。特发性肺纤维化进程伴随着干细胞功能异常,近来研究表明非编码RNA与干细胞功能异常存在联系,进而影响肺纤维化进展。以非编码RNA为靶点的基因疗法暗示了阻断纤维化过程的可能性。目的:总结非编码RNA在特发性肺纤维化干细胞功能异常和治疗中的研究进展。方法:以“IPF,Stem cells,miRNA,lncRNA,circRNA,treatment”为英文检索词,以“特发性肺纤维化、干细胞、miRNA、lncRNA、circRNA、治疗”为中文检索词,检索PubMed、Wiley InterScience、中国知网和万方数据库,范围囊括近10年的文献,然后依据纳入和排除标准进行筛选,最终纳入82篇文献进行分析。结果与结论:①文章首次总结了近年来非编码RNA在特发性肺纤维化的干细胞异常机制中的相关性研究,揭示了miRNA,lncRNA及circRNA共同调控了干细胞的异常激活、分化等活动,并且miRNA常作为后两者作用的中心环节。②现有的临床试验一定程度上肯定了干细胞移植疗法治疗特发性肺纤维化的安全性,但在疗效方面,仅稍改善了患者弥散功能却未能明确缓解纤维化病变的程度,其结果还需要更多设立安慰剂对照的随机试验来验证。③靶向非编码RNA的基因治疗优势在于具有多基因调控特性,可以从上游干预干细胞异常,目前其在体内外实验已取得突破性进展,并被证实与部分药物的作用靶点相关。④然而,特发性肺纤维化基因疗法的缺点是只能产生短期效应,同时其面临着有效剂量、体内稳定性及输送等问题,这些问题还需未来研究进一步解决。⑤总之,虽然非编码RNA疗法自身存在缺陷,但也不失为一种改善肺纤维化干细胞功能异常的新途径,将其与干细胞移植结合,取长补短,可能发挥更好的疗效。
BACKGROUND:With the development of high-throughput technology,non-coding RNAs have gradually attracted attention and are widely involved in the course of various respiratory diseases.The progression of idiopathic pulmonary fibrosis is accompanied by stem cell abnormality and recent studies have shown that non-coding RNAs are associated with stem cell abnormality,thus affecting the progression of pulmonary fibrosis.Gene therapy that targets non-coding RNAs hints at the possibility of blocking the fibrosis process.OBJECTIVE:To summarize the research progress of non-coding RNAs in stem cell dysfunction and treatment of idiopathic pulmonary fibrosis.METHODS:English search terms included“IPF,stem cells,miRNA,lncRNA,circRNA,treatment”and Chinese search terms contained“idiopathic pulmonary fibrosis,stem cells,miRNA,lncRNA,circRNA,treatment”.Databases including PubMed,Wiley InterScience,CNKI,and Wanfang were used for retrieval,covering articles in the past decade.Screening was performed based on the inclusion and exclusion criteria.Finally,82 articles were included for analysis.RESULTS AND CONCLUSION:(1)The recent studies on the correlation between non-coding RNAs and the mechanisms of stem cell abnormality in idiopathic pulmonary fibrosis were summarized,revealing that miRNAs,lncRNAs,and circRNAs jointly regulate the abnormal activation and differentiation of stem cells,and miRNAs are often the central link of the mechanisms of lncRNAs and circRNAs.(2)Existing trials have confirmed the safety of transplantation therapy to a certain extent,but in terms of efficacy,the diffusion function of patients has only been slightly improved,but the degree of fibrosis has not been significantly alleviated.Most importantly,the trials were non-randomized and lack of placebo controls,so more placebo-controlled randomized trials are needed.(3)The most important advantage of non-coding RNA-targeted gene therapy is that it has the characteristics of multi-gene regulation,which can intervene stem cell abnormalities from the upstrea
作者
黄彬
郑金旭
张军
Huang Bin;Zheng Jinxu;Zhang Jun(Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,Jiangsu Province,China;Department of Respiratory and Critical Care Medicine,Affiliated Aoyang Hospital of Jiangsu University,Suzhou 215600,Jiangsu Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第1期130-137,共8页
Chinese Journal of Tissue Engineering Research
基金
镇江市重大项目(SH2018048),项目负责人:郑金旭
苏州市社会发展项目(SYSD2020010),项目负责人:张军。
