miR-141 Regulates colonic leukocytic trafficking by targeting CXCL12β during murine colitis and human Crohn's disease

Huang, Zhen; Shi, Tongguo; Zhou, Qian; Shi, Song; Zhao, Ruihua; Shi, Hao; Dong, Lei; Zhang, Chenyu; Zeng, Ke; Chen, Jiangning; Zhang, Junfeng

doi:10.1136/gutjnl-2012-304213

Cited by 126 publications

(124 citation statements)

References 46 publications

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“…2A). Similarly, the DGMþDOX mice had significantly lower levels of CK (691.84 vs. 1,677.14 U/L), LDH (1,481.63 vs. 2,058.5 U/L), BUN (16.56 vs. 23.89 mmol/L) and ALT (29.57 vs. 69.56 U/L) than WTþDOX mice, indicating that removal of gut microorganisms could effectively prevent the toxicity of doxorubicin to the cardiac (CK and LDH), renal (BUN) and hepatic (ALT) tissues, respectively (Fig. 2B).…”

Section: Endotoxin From Gut Microbiota Causes Inflammation and Tissuementioning

confidence: 84%

Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage

et al. 2016

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Doxorubicin is one of the most effective chemotherapeutic agents used for cancer treatment, but it causes systemic inflammation and serious multiorgan side effects in many patients. In this study, we report that upregulation of the proinflammatory Toll-like receptor TLR4 in macrophages by doxorubicin is an important step in generating its toxic side effects. In patient serum, doxorubicin treatment resulted in leakage of endotoxin and inflammatory cytokines into circulation. In mice, doxorubicin damaged the intestinal epithelium, which also resulted in leakage of endotoxin from the gut flora into circulation. Concurrently, doxorubicin increased TLR4 expression in macrophages both in vitro and in vivo, which further enhanced the sensitivity of these cells to endotoxin. Either depletion of gut microorganisms or blockage of TLR4 signaling effectively decreased doxorubicininduced toxicity. Taken together, our findings suggest that doxorubicin-triggered leakage of endotoxin into the circulation, in tandem with enhanced TLR4 signaling, is a candidate mechanism underlying doxorubicin-induced systemic inflammation. Our study provides new insights for devising relevant strategies to minimize the adverse effects of chemotherapeutic agents such as doxorubicin, which may extend its clinical uses to eradicate cancer cells. Cancer Res; 76(22); 6631-42. Ó2016 AACR.

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Section: Endotoxin From Gut Microbiota Causes Inflammation and Tissuementioning

confidence: 84%

Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage

et al. 2016

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“…Overexpression of miR-146b in DSS-induced colitis mouse via intraperitoneal injection relieved intestinal inflammation and increased the survival rate of mouse [40] . MiR-141 intracolonic administration in the colon of TNBS-induced and IL-10 KO mice regulated leukocyte infiltration and alleviated intestinal inflammation [62] . These data showed the effective ways to administrate miRNAs into human and the possibilities for the future clinical applications of miRNA-based therapeutic approaches in IBD.…”

Section: Future Perspective In Ibd Diagnos-tic and Treatmentmentioning

confidence: 97%

“…Huang et al [62] found up-regulated level of miR-141 was inversely correlated with CXCL12β in the epithelial cells of the inflamed colon tissues from CD patients and mice with experimental colitis.They further demonstrated that miR-141 directly regulated CXCL12β expression and leukocyte migration mediated by CXCL12β. Additionally, overexpression or knockdown of miR-141 in the colon of mice with experimental colitis regulated leukocyte infiltration and alleviated or aggravated intestinal inflammation, respectively.…”

Section: Mirnas Regulate Colonic Epithelial Cell-derived Chemokine Exmentioning

confidence: 99%

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

Chen¹,

Ren²,

Shi³

2014

WJGP

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Inflammatory bowel disease (IBD) is believed to develop via a complex interaction between genetic, environmental factors and the mucosal immune system. Crohn's disease and ulcerative colitis are two major clinical forms of IBD. MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNA molecules, and evolutionary conserved in animals and plants. It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation. MiRNAs are important in many biological processes, such as signal transduction, cellular proliferation, differentiation and apoptosis. Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease, especially IBD. Recent studies have identified altered miRNA profiles in ulcerative colitis, Crohn's disease and inflammatory bowel diseaseassociated colorectal cancer. In addition, emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD. MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway (e.g. , miR-146a, miR-146b, miR-122, miR-132, miR-126), intestinal epithelial barrier function (e.g. , miR-21, miR-150, miR-200b) and the autophagic activity (e.g. , miR-30c, miR-130a, miR-106b, miR-93, miR-196). This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis, their role as disease biomarkers, and perspective for future investigation and clinical application. Key words: Crohn's disease; Inflammatory bowel disease; MicroRNA; Treatment; Ulcerative colitis; Biomarker Core tip: MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that post-transcriptionally regulate gene and protein expression. Recent studies have identified altered miRNA profiles in inflammatory bowel disease (IBD). Special miRNAs which suppress functional targets have been found to play a critical role in regulating key pathogenic mechanism in IBD. In this review, we discuss the possibility to use miRNAs as biomarkers and therapeutic target in IBD.Chen WX, Ren LH, Shi RH. Implication of miRNAs for inflammatory bowel disease treatment: Systematic review. World

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“…Five of these miRNAs were specific for patients in an active stage of CD (miR9, miR126, miR130a, miR181c, and miR375), whereas the remaining 18 were also upregulated in colonic tissues from inactive CD patients. Huang and colleagues [128] identified that miR-141 was downregulated in inflamed colon tissues from active CD patients. miR141 inhibited colonic chemokine CXC ligand 12b expression by directly targeting it and blocked colonic immune cell recruitment.…”

Section: Mirnas In CDmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD.

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miR-141 Regulates colonic leukocytic trafficking by targeting CXCL12β during murine colitis and human Crohn's disease

Cited by 126 publications

References 46 publications

Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage

Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

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