miR‐200b‐containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial‐mesenchymal transition

Yang, Jia; Zhou, Chengzhi; Zhu, Rui; Fan, Huiying; Liu, Xingxing; Duan, Xueyun; Tang, Qing; Shou, Zhexing; Zuo, Dongmei

doi:10.1111/jgh.13797

Cited by 67 publications

(45 citation statements)

References 39 publications

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“…Bone marrow mesenchymal stem cells (BMSCs) transfected with lentivirus to overexpress miR-200b can release EVs packaged with miRNA-200b. The miR-200b-EVs significantly suppressed ZEB1 and ZEB2 to reverse the morphology in TGF-β1-treated IEC-6 cells and ameliorate the TNBS-(2,4,6-trinitrobenzene sulfonic acid-) induced colon fibrosis histologically [129]. EVs secreted by mesenchymal stromal cells (MSCs) have been proposed as important mechanistic relievers in response to cellular inflammation through paracrine effects [130][131][132].…”

Section: The Clinical Potential Of Evs On Treatmentmentioning

confidence: 99%

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Chang

Wang

Zhao

et al. 2020

Mediators of Inflammation

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The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

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Section: The Clinical Potential Of Evs On Treatmentmentioning

confidence: 99%

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Chang

Wang

Zhao

et al. 2020

Mediators of Inflammation

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“…If this mechanism was supported by further studies, potential therapeutic strategies may involve miRNA manipulation. For example, recent work has demonstrated that microvesicle‐delivered miR‐200b reduces colonic fibrosis in TNBS‐induced experimental colitis . Furthermore, preclinical trials that assess the therapeutic impact of targeting miRNAs have already begun .…”

Section: Discussionmentioning

confidence: 99%

“…For example, recent work has demonstrated that microvesicle-delivered miR-200b reduces colonic fibrosis in TNBS-induced experimental colitis. 45 Furthermore, preclinical trials that assess the therapeutic impact of targeting miRNAs have already begun. 46,47 Limitations to therapeutic use of miRNA modulation, include off-target effects [48][49][50]…”

Section: Discussionmentioning

confidence: 99%

Epithelial down‐regulation of the miR‐200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition

Mehta

Lewis

Nijhuis

et al. 2018

J Cellular Molecular Medi

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Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR‐200 family regulates fibrosis‐related EMT in organs other than the gut. E‐cadherin, cytokeratin‐18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) and non‐strictured (NSCD) ileal CD resections and correlated with fibrosis grade. MiR‐200 expression was measured in paired SCD and NSCD tissue compartments using laser capture microdissection and RT‐qPCR. Serum miR‐200 expression was also measured in healthy controls and CD patients with stricturing and non‐stricturing phenotypes. Extra‐epithelial cytokeratin‐18 staining and vimentin‐positive epithelial staining were significantly greater in SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin‐18 staining correlated positively with subserosal fibrosis (P < 0.001). Four miR‐200 family members were down‐regulated in fresh SCD samples (miR‐141, P = 0.002; miR‐200a, P = 0.002; miR‐200c, P = 0.001; miR‐429; P = 0.004); miR‐200 down‐regulation in SCD tissue was localised to the epithelium (P = 0.001‐0.015). The miR‐200 target ZEB1 was up‐regulated in SCD samples (P = 0.035). No difference in serum expression between patient groups was observed. Together, these observations suggest the presence of EMT in CD strictures and implicate the miR‐200 family as regulators. Functional studies to prove this relationship are now warranted.

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“…In a recent study, BMSCs were infected with a miRNA-200b-expressing lentivirus, and MVs were isolated through a differential centrifugation method. The collected MVs were subsequently used to treat TNBS-induced rat intestinal fibrosis [107]. Zhang et al demonstrated the suppressive effect of MVs containing miRNA-29a/c on tumor growth in gastric cancer (GC) [108].…”

Section: Cell-derived Membrane Vesiclesmentioning

confidence: 99%

Recent progress in microRNA-based delivery systems for the treatment of human disease

Chen

Huang

2019

ExRNA

159

118

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MicroRNAs (miRNAs) are naturally occurring, small non-coding RNAs that mediate posttranscriptional regulation. Based on the level of sequence complementarity, miRNAs lead to the degradation of target mRNAs or the suppression of mRNA translation, thereby inhibiting the synthesis of proteins and achieving the regulation of genes. miRNAs, which exhibit tissue-and temporal-specific expression, are important negative regulatory RNAs that decrease the levels of other functional genes. miRNAs play a crucial role in disease progression and prognosis and thus exhibit potential for developing novel therapeutics. Due to the instability of miRNAs and their complex environment, including degradation by nucleases in vivo, the safety and effectiveness of miRNA delivery has become the focus of recent attention. Therefore, we discuss some representative advances related to the application of viral-and nonviral-mediated miRNA delivery systems and provide a new perspective on the future of miRNA-based therapeutic strategies.

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miR‐200b‐containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial‐mesenchymal transition

Abstract: miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2.

Cited by 67 publications

References 39 publications

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Epithelial down‐regulation of the miR‐200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition

Recent progress in microRNA-based delivery systems for the treatment of human disease

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