MicroRNA-132 Modulates Cholinergic Signaling and Inflammation in Human Inflammatory Bowel Disease

Maharshak, Nitsan; Shenhar‐Tsarfaty, Shani; Aroyo, Nimrod; Orpaz, Naama; Guberman, Irene; Canaani, Jonathan; Halpern, Zamir; Dotan, Iris; Berliner, Shlomo; Soreq, Hermona

doi:10.1097/00054725-201212001-00268

Cited by 12 publications

(20 citation statements)

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“…In support of this notion, a variety of previous studies have implicated microRNAs in regulation of the inflammatory response. For example, miR-132 has been shown to be induced in LPS-stimulated human acute monocytic leukemia THP-1 cells [13], peptidoglycan/Tolllike receptor 2-stimulated THP-1 monocytes, human peripheral blood mononuclear cells, primary macrophages [14], and IBD [12], suggestive of a close relationship between miR-132 and the inflammation response.…”

Section: Discussionmentioning

confidence: 99%

“…For example, miR-132 has been shown to attenuate inflammation by targeting AChE mRNA, which leads to enhanced ACh-mediated cholinergic signaling [11]. Moreover, elevated miR-132 levels and lower AChE activity in intestinal biopsies from patients with inflammatory bowel disease (IBD) imply that miR-132 plays an inflammationdependent homeostatic role in IBD patients through regulation of AChE [12]. It remains not known whether miR-132 functions as a protective regulator in sepsis-induced lung injury via the cholinergic anti-inflammatory pathway.…”

Section: Introductionmentioning

confidence: 99%

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miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway

Liu

Jiang

et al. 2015

Experimental Lung Research

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway

Liu

Jiang

et al. 2015

Experimental Lung Research

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“…Other regulatory mechanisms changing cholinesterase activities may also contribute to this decline, such as the AChE mRNA-targeted microRNA-132 (41), which can block AChE gene expression and is upregulated under stress (42) and in intestinal bowel disease (43), yet is drastically reduced in the Alzheimer's disease brain (44). Also relevant are the stress-induced alternative splicing changes (45) and epigenetic potentiation of AChE gene expression, which may explain the longlasting nature of such reactions (46).…”

Section: Discussionmentioning

confidence: 99%

Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

Arbel

Shenhar‐Tsarfaty

Waiskopf

et al. 2013

Mol Med

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Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09-3.15, p = 0.02] and 2.21 [95% CI 1.22-4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

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“…Acetylcholine (ACh) activates its receptor on macrophage through which it interrupts the nuclear translocation of NFκB and suppresses the production of pro-inflammatory cytokines [36] . Maharshak et al [37] found miR-132 had an anti-inflammatory effect on the development of IBD. MiR-132 level was significantly upregulated in biopsies from patients with IBD compared with controls.…”

Section: Pathwaymentioning

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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MicroRNA-132 Modulates Cholinergic Signaling and Inflammation in Human Inflammatory Bowel Disease

Cited by 12 publications

References 0 publications

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway

Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

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