Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs

Abstract

Objective:MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis.Data Sources:Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms “microRNA”, “miR”, “transforming growth factor β”, “tgf β”, “mitogen-activated protein kinase”, “mapk”, “integrin”, “p38”, “c-Jun NH2-terminal kinase”, “jnk”, “extracellular signal-regulated kinase”, “erk”, and “fibrosis”.Study Selection:Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis.Results:Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis, such as immune cell sensitization, effector cell activation, and extracellular matrix remodeling. Moreover, several important molecular signaling pathways involve in fibrosis, such as the transforming growth factor-beta (TGF-β) pathway, mitogen-activated protein kinase (MAPK) pathways, and the integrin pathway are regulated by miRNAs. Third, regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart, lung, liver, and kidney. Interestingly, the actions of many drugs on the human body are also induced by miRNAs. It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways, thereby protecting the structures and functions of different organs.Conclusions:miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases.

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

“…miRNAs miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1 regulate gene expression via the specific binding to target genes (23). Over the past decades, a large number of miRNAs have been identified and are believed to play an important role in the occurrence, differentiation, proliferation and apoptosis of cells (24,25). Recent studies have indicated that alterations in miRNA expression are associated with the occurrence, development, diagnosis and prognosis of cancers (26)(27)(28).…”

MicroRNA in localized scleroderma: a review of literature

“…Makino and co-workers reported that depletion of miRNA-196a level in 3 localized scleroderma skin biopsies was statistically significant compared with 3 keloid skin samples and 3 normal skin biopsies [18]. Consistent with knockdown of microRNA-196a in LoSc skin, the serum concentrations of miRNA-196a were remarkably diminished in patients with localized scleroderma (34) in contrast to healthy controls (22) [18].…”

“…Recent reports have shown that several microRNAs participate in regulation of processes that drive fibrosis, including transforming growth factor (TGF-β) signalling, fibroblast proliferation and differentiation, extracellular matrix proteins deposition and epithelial-to-mesenchymal transition (EMT) [3,18,34]. Upregulation of some profibrotic micro-RNAs results in fibrosis, whereas antifibrotic miRNAs suppress this process and may be knock-down in fibrosis [13].…”

Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016.

“…Particular classes of miRNAs have been identified as strong regulators of fibrotic processes, namely “fibromiRs” and “redoximiRs,” effective genetic regulators of ROS generation (87, 88). Furthermore, miRNAs have also been found to influence various pathways comprising TGF-β, SMADs, and other extracellular matrix (ECM) proteins that are predominantly influential to both universal and organ-specific fibrogenesis (89, 90). …”