Law Ivy Ka Man, Padua David Miguel, Iliopoulos Dimitrios, Pothoulakis Charalabos
Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and.
Center for Systems Biomedicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Am J Physiol Gastrointest Liver Physiol. 2017 Nov 1;313(5):G361-G372. doi: 10.1152/ajpgi.00144.2017. Epub 2017 Aug 3.
G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferases in the cytoplasm, and, thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiological responses in different organs and cell types in humans and animals. Here, we reviewed recent research on GPCR-miRNA interactions related to gastrointestinal pathophysiology, such as inflammatory bowel diseases, irritable bowel syndrome, and gastrointestinal cancers. Given that the presence of different types of cells in the gastrointestinal tract suggests the importance of cell-cell interactions in maintaining gastrointestinal homeostasis, we also discuss how GPCR-miRNA interactions regulate gene expression at the cellular level and subsequently modulate gastrointestinal pathophysiology through molecular regulatory circuits and cell-cell interactions. These studies helped identify novel molecular pathways leading to the discovery of potential biomarkers for gastrointestinal diseases.
G蛋白偶联受体(GPCRs)构成了人类基因组中最大的跨膜受体超家族,几乎在所有胃肠道细胞类型中均有表达。GPCRs与其各自配体的偶联会激活细胞质中的各种磷酸转移酶,因此,肠道中GPCR信号的激活可调节许多细胞和生理过程。对微小RNA(miRNAs)的研究表明,它们是人类和动物不同器官及细胞类型中不同病理生理反应的关键表观遗传调节因子。在此,我们综述了近期有关与胃肠道病理生理学相关的GPCR-miRNA相互作用的研究,如炎症性肠病、肠易激综合征和胃肠道癌症。鉴于胃肠道中存在不同类型的细胞,这表明细胞间相互作用在维持胃肠道稳态方面具有重要性,我们还讨论了GPCR-miRNA相互作用如何在细胞水平上调节基因表达,并随后通过分子调节回路和细胞间相互作用来调节胃肠道病理生理学。这些研究有助于识别导致发现胃肠道疾病潜在生物标志物的新分子途径。