LncRNA KCNA2-AS regulates spinal astrocyte activation through STAT3 to affect postherpetic neuralgia

Cunlong Kong,Fuxing Xu,Huan Ren,Huilian Bu,Chen Huang,Jie Du

doi:10.1186/s10020-020-00232-9

Cunlong Kong, Fuxing Xu + Show 4 more

Open Access

https://doi.org/10.1186/s10020-020-00232-9

Copy DOI

Abstract

ObjectivesPostherpetic neuralgia (PHN) is the most common complication of herpes zoster, but the mechanism of PHN is still unclear. Activation of spinal astrocytes is involved in PHN. Our study aims to explore whether lncRNA KCNA2 antisense RNA (KCNA2-AS) regulates spinal astrocytes in PHN through signal transducers and activators of transcription 3 (STAT3).MethodsVaricella zoster virus (VZV)-infected CV-1 cells were injected into rats to construct a PHN model. Primary spinal cord astrocytes were activated using S-Nitrosoglutathione (GSNO). Glial fibrillary acidic protein (GFAP; marker of astrocyte activation), phosphorylated STAT3 (pSTAT3), and KCNA2-AS were analyzed by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect binding of KCNA2-AS to pSTAT3.ResultsKCNA2-AS was highly expressed in the spinal cord tissue of PHN model rats, and was positively correlated with GFAP expression. GFAP was significantly increased in GSNO-induced cells, but the knockdown of KCNA2-AS reversed this result. Meanwhile, pSTAT3 was significantly increased in GSNO-induced cells, but knockdown of KCNA2-AS reduced pSTAT3 within the nucleus while the total pSTAT3 did not change significantly. pSTAT3 bound to KCNA2-AS and this binding increased with GSNO treatment. Furthermore, knockdown of KCNA2-AS in PHN model rats relieved mechanical allodynia.ConclusionDown-regulation of KCNA2-AS alleviates PHN partly by reducing the translocation of pSTAT3 cytoplasm to the nucleus and then inhibiting the activation of spinal astrocytes.

Highlights

Herpes zoster is an acute infectious skin disease caused by varicella zoster virus (VZV)
KCNA2‐AS was highly expressed in the spinal cord of Postherpetic neuralgia (PHN) model rats, and was correlated with Glial fibrillary acidic protein (GFAP) expression We injected VZV-infected CV-1 cells into rats to construct a PHN rat model, rats were injected with uninfected CV-1 cells as the control group
We detected the mRNA and protein levels of GFAP [a marker of astrocyte activation (Eng and Ghirnikar 1994; Chen 2018)] in the spinal cord tissue, and the results showed that the levels of GFAP mRNA and protein in the PHN group were significantly elevated compared with the sham group (Fig. 1c)

Summary

Introduction

Herpes zoster is an acute infectious skin disease caused by varicella zoster virus (VZV). Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, which occurs in about one in five patients and severely affecting their quality of life (Saguil 2017). The activation of astrocytes has been shown to be a key driver of neuropathic pain Some studies have shown that spinal astrocytes were obviously activated in the PHN model, and the injection of astrocyte-specific inhibitors could obviously alleviate the mechanical allodynia and spinal central sensitization (Zhang 2011; Zhang et al 2009). Inhibiting the activation of spinal astrocytes may be a new therapeutic strategy for PHN

Objectives

Methods

Results

Conclusion