| Literature DB >> 35731374 |
Baoguo Wu1, Congfa Zhou2, Zehao Xiao3, Gan Tang3, Hongmin Guo1, Zihui Hu1, Qixing Hu1, Hao Peng4, Lingzhi Pi4, Zhihua Zhang3, Miaomiao Wang3, Taotao Peng4, Jiaqi Huang3, Shangdong Liang1, Guilin Li5.
Abstract
Diabetic neuropathic pain (DNP) is a common complication of diabetes, and its complicated pathogenesis, as well as clinical manifestations, has brought great trouble to clinical treatment. The spinal cord is an important part of regulating the occurrence and development of DNP. Spinal microglia can regulate the activity of spinal cord neurons and have a regulatory effect on chronic pain. P2Y12 receptor is involved in DNP. P2Y14 and P2Y12 receptors belong to the Gi subtype of P2Y receptors, but there is no report that the P2Y14 receptor is involved in DNP. Closely related to many human diseases, the dysregulation of long noncoding RNA (lncRNA) has the effect of promoting or inhibiting the occurrence and development of diseases. The aim of this research is to investigate the function of the spinal cord P2Y14 receptor in type 2 DNP and to understand the function as well as the possible mechanism of lncRNA-UC.25 + (UC.25 +) in rat spinal cord P2Y14 receptor-mediated DNP. Our results showed that P2Y14 shRNA can reduce the expression of P2Y14 in DNP rats, thereby restraining the activation of microglia, decreasing the expression of inflammatory factors and the level of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. At the same time, UC.25 + shRNA can downregulate the expression of the P2Y14 receptor, reduce the release of inflammatory factors, and diminish the p38 MAPK phosphorylation, indicating that UC.25 + can alleviate spinal cord P2Y14 receptor-mediated DNP. The RNA immunoprecipitation result showed that UC.25 + enriched signal transducers and activators of transcription1 (STAT1) and positively regulated its expression. The chromatin immunoprecipitation result indicated that STAT1 combined with the promoter region of the P2Y14 receptor and positively regulated the expression of the P2Y14 receptor. Therefore, we infer that UC.25 + may alleviate DNP in rats by regulating the expression of the P2Y14 receptor in spinal microglia via STAT1.Entities:
Keywords: Diabetic neuropathic pain; Microglia; P2Y14 receptor; Spinal cord; lncRNA
Mesh：
Substances：
Year: 2022 PMID： 35731374 DOI： 10.1007/s12035-022-02925-0
Source DB: PubMed Journal: Mol Neurobiol ISSN： 0893-7648 Impact factor: 5.682