Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China.
Aging (Albany NY). 2021 Sep 22;13(18):22242-22255. doi: 10.18632/aging.203530.
Focal cerebral ischemia leads to a large number of neuronal apoptosis, and secondary neuronal death is the main cause of cerebral infarction. MicroRNA-21 (miR-21) has been shown to be a strong anti-apoptosis and pro-survival factor in ischemia. However, the precise mechanism of miR-21 in ischemic neuroprotection remains largely unknown. In this study, miR-21 was down-regulated while p53 was up-regulated following ischemia and . Overexpression of miR-21 and substantially inhibited the expression of p53 following ischemia, while inhibition of miR-21 and promoted p53 expression following ischemia. Moreover, the miR-21/p53 axis regulated the expression of Bcl-2/Bax and abolished OGD/R-induced neuronal injury . Furthermore, overexpression of miR-21 reduced neuronal death, protected against ischemic damage, and improved neurological functions by inhibiting p53/Bcl-2/Bax signaling, while inhibition of miR-21 enhanced the p53/Bcl-2/Bax signaling and aggravated the ischemic neuronal injury . Our data uncover a novel mechanism of miR-21 in regulating cerebral ischemic neuronal injury by inhibiting p53/Bcl-2/Bax signaling pathway, which suggests that miR-21/p53 may be attractive therapeutic molecules for treatment of ischemic stroke.
局灶性脑缺血导致大量神经元凋亡,继发性神经元死亡是脑梗死的主要原因。研究表明,微小 RNA-21(miR-21)在缺血中是一种强大的抗细胞凋亡和促生存因子。然而,miR-21 在缺血性神经保护中的精确机制在很大程度上仍然未知。在这项研究中,缺血后 miR-21 下调,而 p53 上调。过表达 miR-21 和 可显著抑制缺血后 p53 的表达,而抑制 miR-21 和 可促进缺血后 p53 的表达。此外,miR-21/p53 轴调节 Bcl-2/Bax 的表达,消除 OGD/R 诱导的神经元损伤。此外,过表达 miR-21 通过抑制 p53/Bcl-2/Bax 信号通路减少神经元死亡,对缺血性损伤起保护作用,并改善神经功能,而抑制 miR-21 增强了 p53/Bcl-2/Bax 信号通路,加重了缺血性神经元损伤。我们的数据揭示了 miR-21 通过抑制 p53/Bcl-2/Bax 信号通路调节脑缺血性神经元损伤的新机制,提示 miR-21/p53 可能是治疗缺血性中风的有吸引力的治疗分子。