Decreased MicroRNA-125a-3p Contributes to Upregulation of p38 MAPK in Rat Trigeminal Ganglions with Orofacial Inflammatory Pain

Dong, Yingchun; Li, Pengfei; Ni, Yanhong; Zhao, Junjie; Liu, Zhiqiang

doi:10.1371/journal.pone.0111594

Cited by 45 publications

(41 citation statements)

References 36 publications

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“…It has been well-documented that activation of p38 MAPK is involved in inflammatory pain [18,28]. An increase in the levels of p-p38, the active form of p38, has been reported in inflammation and neuropathic pain [29–31].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation

2016

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BackgroundThe purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism.Material/MethodsInflammatory pain was induced by injection of complete Freund’s adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4–L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR). In addition, luciferase reporter assay was performed to explore whether RAB23 was a target of miR-16, and qRT-PCR and Western blotting were used to confirm the regulation between RAB23 and miR-16.ResultsThe level of miR-16 was significantly decreased in the CFA-induced inflammatory pain. Intrathecal injection of miR-16 alleviates pain response and raised pain threshold. The level of RAB23 was significantly increased in the pain model, and intrathecal injection of RAB23 aggravated pain response. Luciferase reporter assay confirmed that RAB23 was a direct target of miR-16, and RAB23 was negatively regulated by miR-16. In addition, we found that simultaneous administration of SB203580 and miR-16 further alleviates pain response compared to only administration of miR-16.ConclusionsOur findings suggest that miR-16 relieves chronic inflammatory pain by targeting RAB23 and inhibiting p38 MAPK activation.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation

2016

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“…Neurotrophins (eg NGF, GDNF) that are generated by tissue injury/inflammation are key retrograde messengers that induce changes in gene expression [89,359,360]. Recently, changes in expression of transcription regulating micro RNAs have been demonstrated in DRG and TG in response to peripheral inflammation, and it has been speculated that these contribute to modulating the expression of pro-and/or anti-nociceptive molecules in acute and chronic pain states [361,362]. …”

Section: Neurobiological Changes In Dry Eye Diseasementioning

confidence: 99%

TFOS DEWS II pain and sensation report

et al. 2017

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Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.

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“…MiR-125a-3p is also reported to be involved in early behavioural disorders in stroke-afflicted rats through the regulation of Cadm2 [25] and in THP-1 macrophage differentiation and apoptosis [26]. In addition, miR-125a-3p plays roles in systemic lupus erythematous [27], morbid obesity [28] and orofacial inflammatory pain [29]. Moreover, additional studies on miR-125a-3p need to be performed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-125a-3p affects smooth muscle cell function in vascular stenosis

Chang

Zhang

et al. 2019

Journal of Molecular and Cellular Cardiology

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Many studies have indicated that microRNAs are closely related to the process of peripheral arterial disease (PAD). Previously, we found that microRNA-125a-3p (miR-125a-3p) in restenotic arteries after interventional therapy of lower extremity vessels was notably decreased compared with that of normal control arteries. However, its role in the development of vascular stenosis is not yet clearly understood. The purpose of this study was to investigate the expression, regulatory mechanism and function of miR-125a-3p in the process of vascular stenosis. Methods and results: Quantitative reverse-transcription polymerase chain reaction assays indicated that miR-125a-3p in restenotic arteries after interventional therapy was significantly lower than that in normal control arteries. Immunofluorescence and in situ hybridization co-staining assays in arterial sections demonstrated that miR-125a-3p was mainly expressed in the medial smooth muscle layer. Transfection of miR-125a-3p mimics into cultured vascular smooth muscle cells (VSMCs) effectively inhibited cell proliferation and migration. Then, western blot and luciferase activity assays showed that recombinant human mitogen-activated protein kinase 1 (MAPK1) was a functional target of miR-125a-3p and was involved in miR-125a-3p-mediated cell effects. Finally, the lentiviral infection of miR-125a-3p in balloon-injured rat carotid vascular walls showed that miR-125a-3p overexpression significantly reduced the probability of neointimal membrane production. Conclusions: miR-125a-3p can effectively inhibit the function of VSMCs and the occurrence of vascular stenosis by targeting MAPK1. This study introduces a new molecular mechanism of PAD. We show that regulation of the miR-125a-3p level has the potential to provide a new treatment for PAD and other proliferative vascular diseases. MicroRNAs are highly conserved single-stranded, non-coding RNA

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Decreased MicroRNA-125a-3p Contributes to Upregulation of p38 MAPK in Rat Trigeminal Ganglions with Orofacial Inflammatory Pain

Cited by 45 publications

References 36 publications

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation

TFOS DEWS II pain and sensation report

MicroRNA-125a-3p affects smooth muscle cell function in vascular stenosis

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