LncRNA KCNA2-AS regulates spinal astrocyte activation through STAT3 to affect postherpetic neuralgia
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(2020) 26:113 Kong et al. Mol Med https://doi.org/10.1186/s10020-020-00232-9
Open Access
RESEARCH ARTICLE
LncRNA KCNA2‑AS regulates spinal astrocyte activation through STAT3 to affect postherpetic neuralgia Cunlong Kong1*, Jie Du2, Huilian Bu1, Chen Huang1, Fuxing Xu1 and Huan Ren1
Abstract Objectives: Postherpetic 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). Methods: Varicella 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. Results: KCNA2-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 KCNA2AS reduced pSTAT3 within the nucleus while the total pSTAT3 did not change significantly. pSTAT3 bound to KCNA2AS and this binding increased with GSNO treatment. Furthermore, knockdown of KCNA2-AS in PHN model rats relieved mechanical allodynia. Conclusion: Down-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. Keywords: Postherpetic neuralgia, Spinal astrocytes, LncRNA KCNA2-AS, pSTAT3, GFAP 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 *Correspondence: [email protected] 1 Center of Pain Management, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China Full list of author information is available at the end of the article
prevalence of postherpetic neuralgia increases with age, and 80% of patients are over 50 years old (Yawn and Gilden 2013). Nevertheless, about one-third of patients with PHN do not respond to routine treatment (Gossrau 2014). Therefore, it is necessary to explore new treatment strategies. Astrocytes account for about 20–40% of all glial cells in the central nervous system, and their main role is to provide structural and nutritional support for neurons (Herculano-Houzel 2014). The activation of astrocyte
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