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靶向脊髓损伤中的 miR-21:改变游戏规则?

Targeting miR-21 in spinal cord injuries: a game-changer?

机构信息

Laboratory of Experimental Biochemistry and Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, Via Cristina Belgioioso 173, 20157, Milan, Italy.

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Mol Med. 2022 Sep 23;28(1):118. doi: 10.1186/s10020-022-00546-w.

Abstract

Spinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI.

摘要

脊髓损伤 (SCI) 是一种毁灭性的神经系统疾病,导致身体残疾、心理压力和经济负担。全球每年约有 25 万至 50 万人患有 SCI,其中 60%的患者是 15 至 35 岁的年轻健康男性。SCI 后会发生多种病理情况,如神经炎症、线粒体功能障碍、细胞凋亡、神经胶质瘢痕形成、血脊髓屏障破坏和血管生成破坏,导致恢复受限。 microRNAs (miRs) 是由 22 个核苷酸组成的内源性非编码 RNA,可调节 60%的人类基因,涉及多种正常生理过程和病理情况。miR-21 是表达最高的 miRs 之一,其表达在 SCI 后第一天增加,这种升高可持续至损伤后 28 天。miR-21 的过表达通过抑制神经炎症、改善血脊髓屏障功能、调节血管生成和控制神经胶质瘢痕形成,对 SCI 发挥许多保护作用。它还通过下调 PTEN、Spry2 和 PDCD4 的表达在 SCI 中表现出抗细胞凋亡作用。这篇综述为 miR-21 在 SCI 中的治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f15c/9502625/7ee5b406f99e/10020_2022_546_Fig1_HTML.jpg

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