LncRNA UC.360+shRNA Improves Diabetic Cardiac Sympathetic Dysfunction Mediated by the P2X4 Receptor in the Stellate Ganglion

LncRNA UC.360+shRNA Improves Diabetic Cardiac Sympathetic Dysfunction Mediated by the P2X4 Receptor in the Stellate Ganglion
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LncRNA UC.360 shRNA 改善星状神经节 P2X4 受体介导的糖尿病心脏交感功能障碍

DOI:
10.1021/acschemneuro.1c00050
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发表时间:
2021-03-18
影响因子:
5
通讯作者:
Liang, Shangdong
Liang, Shangdong
中科院分区:
医学3区
文献类型:
--
作者:
Shi, Liran;Sun, Minghao;Liang, Shangdong

文献摘要

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糖尿病心脏自主神经病变(DCAN)是一种并发症,影响超过60%的糖尿病患者。有证据表明P2 X4受体参与DCAN。本研究表明,长链非编码RNA(lncRNA)UC. 360+的表达增加,在星状神经节(SG)的2型糖尿病(DM)大鼠,和原位杂交显示了明确的存在,UC. 360+在SG神经元。应用针对UC. 360 + lncRNA的短发夹RNA(shRNA)技术,进一步探讨UC. 360+在糖尿病大鼠DCAN中的作用及其与SG P2 X4受体的关系。lncRNA UC.360+ shRNA治疗后,糖尿病大鼠心脏交感神经的异常改变得到改善。在这些shRNA处理的DM大鼠的SG中,P2 X4、肿瘤坏死因子-α(TNF-α)、白细胞介素1 β(IL-1 β)和磷酸化ERK 1/2的上调被抑制。因此,lncRNA UC.360+ shRNA处理可以改善SG中由P2 X4受体介导的DCAN。
Diabetic cardiac autonomic neuropathy (DCAN) is a complication that affects more than 60% of diabetic patients. There is evidence for the involvement of P2X4 receptor in DCAN. This study showed that the expression of the long noncoding RNA (lncRNA) UC.360+ was increased in the stellate ganglion (SG) of type 2 diabetes mellitus (DM) rats, and in situ hybridization revealed a clear presence of UC.360+ in SG neurons. The potential roles of UC.360+ in DCAN and its relationship with P2X4 receptor in SG were further explored via application of the short hairpin RNA (shRNA) against lncRNA UC.360+ in DM rats. The abnormal cardiac sympathetic changes in diabetic rats were improved after treatment with lncRNA UC.360+ shRNA. In the SG of these shRNA-treated DM rats, the upregulation of P2X4, tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and phosphorylated ERK1/2 was inhibited. Thus, lncRNA UC.360+ shRNA treatment may improve DCAN mediated by the P2X4 receptor in SG.