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/mib.0b013e318281f47d

Cited by 66 publications

(31 citation statements)

References 37 publications

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“…In human inflammatory bowel disease, miR-132 was found to be a modulator of cholinergic signalling [24]. In MS, miR-132 expression was significantly decreased in circulating CD14 + monocytes [20].…”

Section: Further Myeloid Mirnas With Well Characterized Effectsmentioning

confidence: 99%

Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Gilicze

Wiener

Tóth

et al. 2014

BioMed Research International

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In the past few years expanding knowledge has been accumulated about the role of microRNAs (miRNAs) not only in hematopoiesis and cancer, but also in inflammatory and infectious diseases. Regarding myeloid cells, our knowledge is relatively insufficient, therefore we intended to collect the available data of miRNA profiles of myeloid cells. In addition to a rather general myeloid regulator miR-223, two other miRNAs seem to be useful subjects in understanding of myeloid miRNA biology: miR-27a and miR-652. We review functions of these three miRNAs and other myeloid miRNAs focusing on their roles in monocytes, neutrophils, eosinophils, basophils and mast cells.

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Section: Further Myeloid Mirnas With Well Characterized Effectsmentioning

confidence: 99%

Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Gilicze

Wiener

Tóth

et al. 2014

BioMed Research International

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“…This regulation is disturbed in numerous syndromes, including Alzheimer's disease (12), inflammatory bowel disease (13) and acute stress (14), suggesting that inherited and/or acquired interference with AChE-targeted miRs may change the outcome of diverse anxiety and inflammation-related diseases. Recently, we identified the primate-specific miR-608 (14) as a potential AChE-targeting miRNA.…”

Section: Introductionmentioning

confidence: 99%

Competing targets of microRNA-608 affect anxiety and hypertension

Hanin

Shenhar‐Tsarfaty

Yayon

et al. 2014

Human Molecular Genetics

105

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MicroRNAs (miRNAs) can repress multiple targets, but how a single de-balanced interaction affects others remained unclear. We found that changing a single miRNA–target interaction can simultaneously affect multiple other miRNA–target interactions and modify physiological phenotype. We show that miR-608 targets acetylcholinesterase (AChE) and demonstrate weakened miR-608 interaction with the rs17228616 AChE allele having a single-nucleotide polymorphism (SNP) in the 3′-untranslated region (3′UTR). In cultured cells, this weakened interaction potentiated miR-608-mediated suppression of other targets, including CDC42 and interleukin-6 (IL6). Postmortem human cortices homozygote for the minor rs17228616 allele showed AChE elevation and CDC42/IL6 decreases compared with major allele homozygotes. Additionally, minor allele heterozygote and homozygote subjects showed reduced cortisol and elevated blood pressure, predicting risk of anxiety and hypertension. Parallel suppression of the conserved brain CDC42 activity by intracerebroventricular ML141 injection caused acute anxiety in mice. We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream effects changing important biological pathways.

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“…Patients with inflammatory bowel diseases show significantly lower AChE activity and correspondingly higher levels of miRNA-132, a post-transcriptional inhibitor of AChE [101]. Interestingly, patients with Crohn's disease or ulcerative colitis differ in their response to nicotine.…”

Section: Digestive Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

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Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule that can be released by and act on non-neuronal cells. In these cells the system of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is termed the non-neuronal cholinergic system (NNCS). There is increasing evidence that the NNCS is dysregulated in various diseases and can have an influence on their pathology. However, for many organ systems not much is known about the expression and function of the NNCS. Thus, this review focusses on the role of the NNCS in different organ systems in health and disease. Dysregulation of ACh synthesis and release, mutations or polymorphisms in genes encoding NNCS components, and auto-antibodies against NNCS components are common factors influencing disease progression. Pharmacological agents targeting the NNCS are already successfully in clinical use for some disorders, indicating that interfering with this system is very promising and more research is needed to elucidate the role of the NNCS in different tissues and pathological states.

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

Abstract: Taken together, these findings support an inflammation-dependent homeostatic role for the regulation by miR-132 of AChE in IBD, opening new venues for therapeutic interference.

Cited by 66 publications

References 37 publications

Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation

Competing targets of microRNA-608 affect anxiety and hypertension

The Non-Neuronal Cholinergic System in Health and Disease

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