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MicroRNA 在炎症性肠病中的作用:临床证据和临床前动物模型的发展。

Role of MicroRNA in Inflammatory Bowel Disease: Clinical Evidence and the Development of Preclinical Animal Models.

机构信息

Department of Bioengineering, Northeastern University, Boston, MA 02115, USA.

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

出版信息

Cells. 2021 Aug 26;10(9):2204. doi: 10.3390/cells10092204.

Abstract

The dysregulation of microRNA (miRNA) is implicated in cancer, inflammation, cardiovascular disorders, drug resistance, and aging. While most researchers study miRNA's role as a biomarker, for example, to distinguish between various sub-forms or stages of a given disease of interest, research is also ongoing to utilize these small nucleic acids as therapeutics. An example of a common pleiotropic disease that could benefit from miRNA-based therapeutics is inflammatory bowel disease (IBD), which is characterized by chronic inflammation of the small and large intestines. Due to complex interactions between multiple factors in the etiology of IBD, development of therapies that effectively maintain remission for this disease is a significant challenge. In this review, we discuss the role of dysregulated miRNA expression in the context of clinical ulcerative colitis (UC) and Crohn's disease (CD)-the two main forms of IBD-and the various preclinical mouse models of IBD utilized to validate the therapeutic potential of targeting these miRNA. Additionally, we highlight advances in the development of genetically engineered animal models that recapitulate clinical miRNA expression and provide powerful preclinical models to assess the diagnostic and therapeutic promise of miRNA in IBD.

摘要

miRNA(微 RNA)的失调与癌症、炎症、心血管疾病、耐药性和衰老有关。虽然大多数研究人员研究 miRNA 作为生物标志物的作用,例如,区分特定疾病的不同亚型或阶段,但也在进行研究以利用这些小核酸作为治疗剂。可以从 miRNA 治疗中受益的常见多效性疾病的一个例子是炎症性肠病 (IBD),其特征是小肠和大肠的慢性炎症。由于 IBD 的病因中存在多种因素的复杂相互作用,因此开发有效维持该疾病缓解的疗法是一个重大挑战。在这篇综述中,我们讨论了失调的 miRNA 表达在临床溃疡性结肠炎 (UC) 和克罗恩病 (CD)-IBD 的两种主要形式-的背景下的作用,以及用于验证针对这些 miRNA 的治疗潜力的各种 IBD 临床前小鼠模型。此外,我们强调了遗传工程动物模型的发展进展,这些模型再现了临床 miRNA 表达,并提供了强大的临床前模型,以评估 miRNA 在 IBD 中的诊断和治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24fb/8468560/17b4c68aa2bb/cells-10-02204-g001.jpg

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