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微小RNA在肠-脑相互作用紊乱中的作用:临床见解与治疗选择

Role of microRNAs in Disorders of Gut-Brain Interactions: Clinical Insights and Therapeutic Alternatives.

作者信息

Singh Rajan, Zogg Hannah, Ro Seungil

机构信息

Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, 1664 North Virginia Street, Reno, NV 89557, USA.

出版信息

J Pers Med. 2021 Oct 12;11(10):1021. doi: 10.3390/jpm11101021.

Abstract

Disorders of gut-brain interactions (DGBIs) are heterogeneous in nature and intertwine with diverse pathophysiological mechanisms. Regular functioning of the gut requires complex coordinated interplay between a variety of gastrointestinal (GI) cell types and their functions are regulated by multiple mechanisms at the transcriptional, post-transcriptional, translational, and post-translational levels. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by binding to specific mRNA targets to repress their translation and/or promote the target mRNA degradation. Dysregulation of miRNAs might impair gut physiological functions leading to DGBIs and gut motility disorders. Studies have shown miRNAs regulate gut functions such as visceral sensation, gut immune response, GI barrier function, enteric neuronal development, and GI motility. These biological processes are highly relevant to the gut where neuroimmune interactions are key contributors in controlling gut homeostasis and functional defects lead to DGBIs. Although extensive research has explored the pathophysiology of DGBIs, further research is warranted to bolster the molecular mechanisms behind these disorders. The therapeutic targeting of miRNAs represents an attractive approach for the treatment of DGBIs because they offer new insights into disease mechanisms and have great potential to be used in the clinic as diagnostic markers and therapeutic targets. Here, we review recent advances regarding the regulation of miRNAs in GI pacemaking cells, immune cells, and enteric neurons modulating pathophysiological mechanisms of DGBIs. This review aims to assess the impacts of miRNAs on the pathophysiological mechanisms of DGBIs, including GI dysmotility, impaired intestinal barrier function, gut immune dysfunction, and visceral hypersensitivity. We also summarize the therapeutic alternatives for gut microbial dysbiosis in DGBIs, highlighting the clinical insights and areas for further exploration. We further discuss the challenges in miRNA therapeutics and promising emerging approaches.

摘要

肠-脑相互作用障碍(DGBIs)本质上具有异质性,且与多种病理生理机制相互交织。肠道的正常运作需要多种胃肠道(GI)细胞类型之间进行复杂的协调相互作用,其功能在转录、转录后、翻译和翻译后水平受到多种机制的调节。微小RNA(miRNA)是小的非编码RNA分子,通过与特定的mRNA靶标结合来转录后调节基因表达,从而抑制其翻译和/或促进靶标mRNA降解。miRNA的失调可能会损害肠道生理功能,导致DGBIs和肠道运动障碍。研究表明,miRNA可调节肠道功能,如内脏感觉、肠道免疫反应、胃肠道屏障功能、肠神经元发育和胃肠道运动。这些生物学过程与肠道高度相关,其中神经免疫相互作用是控制肠道稳态的关键因素,功能缺陷会导致DGBIs。尽管广泛的研究已经探索了DGBIs的病理生理学,但仍有必要进一步研究以加强这些疾病背后分子机制的研究。miRNA的治疗靶向代表了一种有吸引力的DGBIs治疗方法,因为它们为疾病机制提供了新的见解,并且在临床上作为诊断标志物和治疗靶点具有巨大的应用潜力。在这里,我们综述了关于miRNA在胃肠道起搏细胞、免疫细胞和肠神经元中调节DGBIs病理生理机制的最新进展。本综述旨在评估miRNA对DGBIs病理生理机制的影响,包括胃肠道运动障碍、肠道屏障功能受损、肠道免疫功能障碍和内脏超敏反应。我们还总结了DGBIs中肠道微生物群失调的治疗选择,强调了临床见解和进一步探索的领域。我们进一步讨论了miRNA治疗中的挑战和有前景的新兴方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bd3/8541612/391ee3229a31/jpm-11-01021-g001.jpg

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