Critical roles of microRNAs in the pathogenesis of systemic sclerosis: New advances, challenges and potential directions

Miao, Cheng-gui; Xiong, You-yi; Yu, Hao; Zhang, Xiao-lin; Qin, Mei-song; Song, Tong-wen; Du, Chuan-lai

doi:10.1016/j.intimp.2015.07.042

Cited by 24 publications

(18 citation statements)

References 98 publications

(99 reference statements)

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“…Recent studies have also highlighted the role microRNA (miRNA) in SSc pathogenesis. Differentially expressed miRNAs that target both inflammation and fibrosis have been identified in SSc . These miRNAs may be either anti‐ or pro‐fibrotic.…”

Section: Resultsmentioning

confidence: 99%

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Kumar

Singh

Rattan

et al. 2017

Aliment Pharmacol Ther

108

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SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion Despite extensive investigation the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions.

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Section: Resultsmentioning

confidence: 99%

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Kumar

Singh

Rattan

et al. 2017

Aliment Pharmacol Ther

108

View full text Add to dashboard Cite

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“…miRNAs are small non-coding RNAs containing about 22 nucleotides, which are post-transcriptional repressors of gene function ( 139 ). miRNAs have been recently reported to play important roles in SSc pathogenesis as well as in the EndMT process ( 140 , 141 ). However, further studies are required to determine whether the SSc-associated profibrotic or antifibrotic effects of specific miRNAs are mediated by EndoMT.…”

Section: Introductionmentioning

confidence: 99%

A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis

et al. 2018

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Systemic sclerosis (SSc), an autoimmune disease that is associated with a number of genetic and environmental risk factors, is characterized by progressive fibrosis and microvasculature damage in the skin, lungs, heart, digestive system, kidneys, muscles, joints, and nervous system. These abnormalities are associated with altered secretion of growth factor and profibrotic cytokines, such as transforming growth factor-beta (TGF-β), interleukin-4 (IL-4), platelet-derived growth factor (PDGF), and connective-tissue growth factor (CTGF). Among the cellular responses to this proinflammatory environment, the endothelial cells phenotypic conversion into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndMT), has been postulated. Reactive oxygen species (ROS) might play a key role in SSs-associated fibrosis and vascular damage by mediating and/or activating TGF-β-induced EndMT, a phenomenon that has been observed in other disease models. In this review, we identified and critically appraised published studies investigating associations ROS and EndMT and the presence of EndMT in SSc, highlighting a potential link between oxidative stress and EndMT in this condition.

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“…miRNAs are a class of non-coding single-stranded small RNA nucleotides from pri-miRNA processing by Drosha and Dicer (19). Typically, miRNAs can recognize specific mRNAs, and bind to their 3'-UTR by inexact match, affecting mRNA stability, or inhibit their translation, regulating the expression levels of target genes (20)(21)(22). Studies on miRNA functions are mainly achieved with the usage of in vitro miRNA mimics.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑146a promotes proliferation and migration of AOB‑treated embryoid body via PDGFRA induction

Zhu

Liu

et al. 2017

Mol Med Report

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Antioxidant of bamboo leaves (AOB) has been proven to have antioxidant activity and an inhibitory effect on free radicals that induce deterioration of macromolecules. The multi‑target regulation of microRNAs (miRs) in the complicated process of vasculogenesis and angiogenesis lead to the use of miRNA therapy in vascular development. In the present study, the role of miRNAs on early embryo vascular development upon AOB stimulation was investigated. For this purpose, mouse embryonic stem cells were spontaneously differentiated as embryoid bodies (EBs) and were examined by phase contrast microscopy. miR‑146a mimic and scramble control were transfected into EBs and potential targets of miR‑146a were predicted. Cell proliferation and migration were detected by cell viability and wound‑healing and migration assays, respectively. Angiogenesis was determined by the Spheroid sprouting assay. It was demonstrated that EBs transfected with miR‑146a mimic had an increased growth rate compared with the control cells. miR‑146a‑transfected cells were very susceptible to AOB treatment. Furthermore, among the predicted miR‑146a targets, platelet‑derived growth factor receptor alpha (PDGFRA) was identified as a bona fide target of miR‑146a. In conclusion, PDGFRA was demonstrated to participate in the modulation of cell migration and proliferation of mouse EBs. The present study expanded the current understanding of AOB biology and elucidated the mechanisms underlying early embryo vascular development upon AOB stimulation.

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Critical roles of microRNAs in the pathogenesis of systemic sclerosis: New advances, challenges and potential directions

Cited by 24 publications

References 98 publications

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis

Downregulation of miR‑146a promotes proliferation and migration of AOB‑treated embryoid body via PDGFRA induction

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