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鸟瞰囊性纤维化:一种被低估的多方面慢性疾病。

A bird eye view on cystic fibrosis: An underestimated multifaceted chronic disorder.

机构信息

Department of Immunology and Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.

Department of Immunology and Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.

出版信息

Life Sci. 2021 Mar 1;268:118959. doi: 10.1016/j.lfs.2020.118959. Epub 2020 Dec 28.

Abstract

Cystic fibrosis (CF) is an autosomal recessive disease which involves the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF involves in the inflammatory processes and is considered as a multisystem disorder that is not confined to lungs, but it also affects other vital organs that leads to numerous co-morbidities. The respiratory disorder in the CF results in mortality and morbidity which is characterized by series of serious events involving mucus hypersecretion, microbial infections, airways obstruction, inflammation, destruction of epithelium, tissue remodeling and terminal lung diseases. Mucins are the high molecular weight glycoproteins important for the viscoelastic properties of the mucus, play a significant role in the disease mechanisms. Determining the functional association between the CFTR and mucins might help to identify the putative target for specific therapeutic approach. In fact, furin enzyme which helps in the entry of novel COVID-19 virus into the cell, is upregulated in CF and this can also serve as a potential target for CF treatment. Moreover, the use of nano-formulations for CF treatment is an area of research being widely studied as they have also demonstrated promising outcomes. The in-depth knowledge of non-coding RNAs like miRNAs and lncRNAs and their functional association with CFTR gene expression and mutation can provide a different range of opportunity to identify the promising therapeutic approaches for CF.

摘要

囊性纤维化(CF)是一种常染色体隐性疾病,涉及囊性纤维化跨膜电导调节因子(CFTR)基因突变。CF 涉及炎症过程,被认为是一种多系统疾病,不仅限于肺部,还会影响其他重要器官,导致多种合并症。CF 导致的呼吸障碍导致死亡率和发病率,其特征是一系列严重事件,包括粘液过度分泌、微生物感染、气道阻塞、炎症、上皮细胞破坏、组织重塑和终末期肺病。粘蛋白是高分子量糖蛋白,对粘液的粘弹性特性很重要,在疾病机制中发挥重要作用。确定 CFTR 和粘蛋白之间的功能关联可能有助于确定针对特定治疗方法的潜在靶标。事实上,CF 中上调的凝乳酶原激活酶(furin enzyme)有助于新型 COVID-19 病毒进入细胞,这也可以作为 CF 治疗的潜在靶标。此外,纳米制剂在 CF 治疗中的应用是一个广泛研究的研究领域,因为它们也显示出有希望的结果。对非编码 RNA(如 miRNA 和 lncRNA)的深入了解及其与 CFTR 基因表达和突变的功能关联,可以为 CF 提供不同范围的有希望的治疗方法。

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