Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathi
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(2020) 26:104 Li et al. Mol Med https://doi.org/10.1186/s10020-020-00235-6
Open Access
RESEARCH ARTICLE
Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury‑induced neuropathic pain in rats by targeting miR‑133a‑3p/SRPK1 axis Zhen Li1, Aiyuan Li1, Liping Yan1, Tian Yang1, Wei Xu1 and Pengju Fan2*
Abstract Background: Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models. Methods: We first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin‐6 (IL-6), tumor necrosis factor‐α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays. Results: Our findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL‐6, IL‐1β and TNF‐α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats. Conclusion: DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression. Keywords: DLEU1, miR-133a-3p, SRPK1, Neuropathic pain
*Correspondence: [email protected] 2 Department of Burn and Plastic Surgery, Xiangya Hospital Central South University, No. 87 Xiangya Road, Kaifu District, Changsha 410008, Hunan, China Full list of author information is available at the end of the article
Introduction Neuropathic pain, a chronic pain caused by nerve lesions or dysfunction, has become the most challenging neurological disease around the world. Neuropathic pain is related to hyperalgesia and dysphonia. More than 20% of cancer pain has close association with neuropathic pain (Bouhassira et al. 2008; Hecke et al. 2014). Neuropathic pain affects many people in the world. However,
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