NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease

Ghorpade, Devram Sampat; Sinha, Akhuri Yash; Holla, Sahana; Singh, Vikas; Balaji, Kithiganahalli Narayanaswamy

doi:10.1074/jbc.m113.492496

Cited by 77 publications

(65 citation statements)

References 43 publications

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“…A miRs NOD interaction has been implicated in IBD. These miRNAs include miR29 [65] , miR122 [66] , miR146a [67] , and miR192 [68] . For example, polymorphisms in NOD2 impair miR29 expression in DCs, and this results in exaggerated IL-23-induced inflammation [65] .…”

Section: Nod-like Receptorsmentioning

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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Section: Nod-like Receptorsmentioning

confidence: 99%

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

Zhang

2016

WJG

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“…NOD2 can be activated by muramyl dipeptide (MDP), a component of bacterial cell wall, which induces the activation of NF-κB [22] . MiR-146a was reported to regulate gut inflammation via NOD2-sonic hedgehog (SHH) signaling [23] . SHH signaling is an important pathway that maintains gut homeostasis and directs gut development.…”

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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“…N ucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pathogen sensor that is not only effective in eliciting immune responses against the invading pathogens but also has evolved as a critical regulator of multiple inflammatory disorders (1)(2)(3). For example, allelic variants of Nod2 were found to be associated with inflammatory bowel diseases, such as Crohn's disease (4,5), and mutations in a single amino acid of NOD2 causes inflammatory arthritis disease, such as Blau syndrome (6)(7)(8)(9). Although the etiology of inflammatory arthritis or acute arthritis is not very clear, they are often characterized by the presence of proinflammatory cytokines, such as IL-1b and IL-6, in the joints (7,10).…”

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confidence: 99%

WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice

Singh

Holla

Ramachandra

et al. 2015

The Journal of Immunology

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In addition to its role in innate immunity, the intracellular pathogen sensor nucleotide-binding oligomerization domain 2 (NOD2) has been implicated in various inflammatory disorders, including the development of acute arthritis. However, the molecular mechanisms involved in the development of NOD2-responsive acute arthritis are not clear. In this study, we demonstrate that NOD2 signals to a cellular protein, Ly6/PLAUR domain–containing protein 6, in a receptor-interacting protein kinase 2–TGF-β–activated kinase 1–independent manner to activate the WNT signaling cascade. Gain- or loss-of-function of the WNT signaling pathway in an in vivo experimental mouse arthritis model or in vitro systems established the role for WNT-responsive X-linked inhibitor of apoptosis during the development of acute arthritis. Importantly, WNT-stimulated X-linked inhibitor of apoptosis mediates the activation of inflammasomes. The subsequent caspase-1 activation and IL-1β secretion together contribute to the phenotypic character of the inflammatory condition of acute arthritis. Thus, identification of a role for WNT-mediated inflammasome activation during NOD2 stimulation serves as a paradigm to understand NOD2-associated inflammatory disorders and develop novel therapeutics.

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NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease

Cited by 77 publications

References 43 publications

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

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

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice

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