Dataset Information

Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway.

ABSTRACT: Long noncoding RNAs (lncRNAs) have been involved in the development of multiple pathological processes including neuropathic pain. The aim of the present study is to investigate the role of lncRNA down-regulated in liver cancer stem cells (DILC) in the progression of neuropathic pain and its underlying mechanism. Neuropathic pain rat model was established with the bilateral chronic constriction injury (bCCI) method. The results from quantitative PCR analysis in the spinal cord showed that DILC was significantly up-regulated in rats with bCCI compared with the sham group. DILC down-regulation mediated by intrathecal administration of DILC siRNA significantly increased the mechanical shrinkage threshold (MWT) and paw withdrawal threshold latency (PWTL), decreased the positive frequency for nerve sensitivity to cold and suppressed the expression of inflammatory genes in bCCI rats. Down-regulation of DILC induced suppressor of cytokine signaling (SOCS3) expression and inhibited the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in spinal cord tissues. Western blotting showed that down-regulation of DILC by DILC siRNA transfection induced SOCS3 expression and inhibited the expression of p-Janus kinase 2 (p-JAK2) and p-STAT3 and their downstream genes in primary microglia. Furthermore, down-regulation of DILC increased the viability of primary microglia, suppressed apoptosis, and inhibited the production of interleukin (IL)-6 and IL-1? in microglia. In contrast, overexpression of DILC showed the opposite functions to those of DILC knockdown. In conclusion, silence of lncRNA DILC attenuates neuropathic pain via SOCS3-induced suppression of the JAK2/STAT3 pathway.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7300282 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway.

Liu Yujie Y Feng Lu L Ren Shichao S Zhang Yingxiu Y Xue Jing J

Bioscience reports 20200601 6

Long noncoding RNAs (lncRNAs) have been involved in the development of multiple pathological processes including neuropathic pain. The aim of the present study is to investigate the role of lncRNA down-regulated in liver cancer stem cells (DILC) in the progression of neuropathic pain and its underlying mechanism. Neuropathic pain rat model was established with the bilateral chronic constriction injury (bCCI) method. The results from quantitative PCR analysis in the spinal cord showed that DILC w ...[more]

PMID: 32510145

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Project description:BackgroundVentilator-induced lung injury (VILI) is characterized by vascular barrier dysfunction and suppression of alveolar fluid clearance (AFC). Obesity itself leads to chronic inflammation, which may initiate an injurious cascade to the lungs and simultaneously induce a protective feedback. In this study, we investigated the protective mechanism of obesity on VILI in a mouse model.MethodsThe VILI model was set up via 6-h mechanical ventilation with a high tidal volume. Parameters including lung injury score, STAT3/NFκB pathway, and AFC were assessed. Mice with diet-induced obesity were obtained by allowing free access to a high-fat diet since the age of 3 weeks. After a 9-week diet intervention, these mice were sacrificed at the age of 12 weeks. The manipulation of SOCS3 protein was achieved by siRNA knockdown and pharmaceutical stimulation using hesperetin. WNK4 knockin and knockout obese mice were used to clarify the pathway of AFC modulation.ResultsObesity itself attenuated VILI. Knockdown of SOCS3 in obese mice offset the protection against VILI afforded by obesity. Hesperetin stimulated SOCS3 upregulation in nonobese mice and provided protection against VILI. In obese mice, the WNK4 axis was upregulated at the baseline, but was significantly attenuated after VILI compared with nonobese mice. At the baseline, the manipulation of SOCS3 by siRNA and hesperetin also led to the corresponding alteration of WNK4, albeit to a lesser extent. After VILI, WNK4 expression correlated with STAT3/NFκB activation, regardless of SOCS3 status. Obese mice carrying WNK4 knockout had VILI with a severity similar to that of wild-type obese mice. The severity of VILI in WNK4-knockin obese mice was counteracted by obesity, similar to that of wild-type nonobese mice only.ConclusionsObesity protects lungs from VILI by upregulating SOCS3, thus suppressing the STAT3/NFκB inflammatory pathway and enhancing WNK4-related AFC. However, WNK4 activation is mainly from direct NFκB downstreaming, and less from SOCS3 upregulation. Moreover, JAK2-STAT3/NFκB signaling predominates the pathogenesis of VILI. Nevertheless, the interaction between SOCS3 and WNK4 in modulating VILI in obesity warrants further investigation.

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Dataset Information

Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway.

Publications

Inhibition of lncRNA DILC attenuates neuropathic pain via the SOCS3/JAK2/STAT3 pathway.

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