MicroRNA-21 targets the vitamin D–dependent antimicrobial pathway in leprosy

Liu, Philip T.; Wheelwright, Matthew; Teles, Rosane M. B.; Komisopoulou, Evangelia; Edfeldt, Kristina; Ferguson, Benjamin G.; Mehta, Manali; Vazirnia, Aria; Rea, Thomas H.; Sarno, Euzenir Nunes; Graeber, Thomas G.; Modlin, Robert L.

doi:10.1038/nm.2584

Cited by 188 publications

(197 citation statements)

References 25 publications

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“…An increasing body of evidence shows that miRNAs play fundamental roles in neurogenesis, neuron survival, dendritic outgrowth and spine formation (29)(30)(31). Aberrant miRNA expression has also been linked to a variety of diseases, including several nervous system diseases (32)(33)(34). For example, miR-219 modulates N-methyl-D-aspartate (NMDA) receptor-mediated neurobehavioral dysfunction, which is implicated in schizophrenia and autism (35), and the expression of the sensory organ-specific miR-183 family has been shown to be altered following spinal nerve ligation (14).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Chronic neuropathic pain is associated with global changes in gene expression in different areas of the nociceptive pathway. MicroRNAs (miRNAs) are small (~22 nt long) noncoding RNAs, which are able to regulate hundreds of different genes post-transcriptionally. The aim of this study was to determine the miRNA expression patterns in the different regions of the pain transmission pathway using a rat model of human neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI). Using microarray analysis and quantitative reverse transcriptase-PCR, we observed a significant upregulation in miR-341 expression in the dorsal root ganglion (DRG), but not in the spinal dorsal horn (SDH), hippocampus or anterior cingulate cortex (ACC), in the rats with neuropathic pain compared to rats in the naïve and sham-operated groups. By contrast, the expression of miR-203, miR-181a-1 * and miR-541 * was significantly reduced in the SDH of rats with neuropathic pain. Our data indicate that miR-341 is upregulated in the DRG, whereas miR-203, miR-181a-1 * and miR-541 * are downregulated in the SDH under neuropathic pain conditions. Thus, the differential expression of miRNAs in the nervous system may play a role in the development of chronic pain. These observations may aid in the development of novel treatment methods for neuropathic pain, which may involve miRNA gene therapy in local regions. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting either the peripheral or central nervous system (1,2). Although pain has been investigated in depth for decades, neuropathic pain is still frequently under-treated (3), due to poor understanding of its pathophysiological and molecular mechanisms. Several regions of the nociceptive pathway, including the anterior cingulate cortex (ACC), hippocampus, spinal dorsal horn (SDH) and dorsal root ganglion (DRG), are involved in the development and maintenance of neuropathic pain (4-9). Several recent studies have shown that peripheral and central sensitization are associated with global changes in gene expression in different regions of the pain transmission pathway, and that these changes may be part of the mechanisms behind neuropathic pain (10-13). In order to elucidate the molecular mechanisms underlying neuropathic pain, it is essential to determine how gene expression patterns are altered by nerve injuries and how these alterations lead to the development and maintenance of chronic pain.miRNAs are a large class of short non-coding RNAs (~22 nt long), many of which are expressed either predominantly or exclusively in the nervous system (14-21). Furthermore, changes (either increases or decreases) in miRNA expression have been found in many disease states (22-24). Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold all...

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Section: Discussionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

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“…The most recent studies have included interferon (Teles et al 2013), vitamin D-dependent antimicrobial pathways (Liu et al 2012), NOD2-mediated signalling (Netea et al 2010) and the role of T regulatory cells, Th-17/IL17a/IL-17F cytokines, CD163 and galectin-3 (Polycarpou et al 2013). A deeper understanding of the M. leprae genome will provide insight into the mechanism by which this organism avoids immune surveillance.…”

Section: Discussionmentioning

confidence: 99%

Importance of the immune response to Mycobacterium leprae in the skin

Jin

Ahn

2018

biomed dermatol

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The causative agent of leprosy is Mycobacterium leprae (M. leprae), which establishes infectious lesions in the skin. Leprosy is classified based on the clinical manifestation, the host's immune response and skin symptoms. M. leprae is an intracellular pathogen that invades keratinocytes, macrophages, dendritic cells and Schwann cells and replicates within these cells. M. leprae-infected keratinocytes secrete various cytokines and chemokines and induce highly effective immune responses. Understanding the mechanisms by which M. leprae establishes an infection within the skin and the associated immune response may be of great help in the early detection and treatment of the disease.

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“…In turn, bacteria have evolved mechanisms to alter and evade the host immune response [11]. Pathogens slow the innate immune defenses by down-regulating the VDR [12][13][14], for example Mycobacterium tuberculosis, Mycobacterium Leprae, and Aspergillus Fumigate down-regulate VDR activity. This action allows intracellular bacteria to persist in the cytoplasm of nucleated cells and increases susceptibility to other diseases [15].…”

Section: Discussionmentioning

confidence: 99%

Metadichol® and MRSA Infections: A Case Report

Raghavan¹

2017

J Infect Dis Ther

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Metadichol ® [1] is a Nanoemulsion of long-chain alcohols called as Policosanol and is present in foods such as rice, sugar cane, wheat, and peanuts. Metadichol ® acts on Nuclear Vitamin D receptors (VDR) that have a ubiquitous presence in cells and tissues of the body to stimulate the immune system and inhibit a variety of disease processes, resulting from viral, bacterial and parasitic infections. Infectious agents can cause disease by avoiding normal host defense mechanisms or by subverting them to promote their replication. They do so by blocking VDR receptor that is responsible for innate immunity, and this suppression of the immune response leads to persistent infections.We present a case study of a patient who had acquired MRSA infections and how Metadichol ® by its actions on the VDR has resolved the problem of this deadly disease without any side effects.

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MicroRNA-21 targets the vitamin D–dependent antimicrobial pathway in leprosy

Cited by 188 publications

References 25 publications

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Importance of the immune response to Mycobacterium leprae in the skin

Metadichol® and MRSA Infections: A Case Report

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