Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin Province, China.
Department of Neonatology, The Second Hospital of Jilin University, Changchun, 130041, Jilin Province, China.
Brain Res Bull. 2021 Mar;168:146-155. doi: 10.1016/j.brainresbull.2020.12.006. Epub 2020 Dec 14.
A large number of studies have shown that stem cells from human exfoliated deciduous teeth (SHED) has a protective effect on brain damage, but its specific mechanism is unclear. This research focused on the effect of microRNA (miR)-26a that transmitted by SHED in intracerebral hemorrhage (ICH).
SHED were extracted from deciduous teeth of healthy children and miR-26a expression in SHED was altered through transfection, and then the SHED were conducted with neuron differentiated induction, expression of β3 tubulin, MAP-2 and glial fibrillary acidic protein (GFAP), number of dendritic spines and cell proliferation were detected. ICH rat models were established by stereotactic injection of collagenase VII into the left striatum and the modeled rats were injected with miR-26a mimic or inhibitor-transfected SHED suspension. Then, the brain water content, blood-brain barrier permeability, pathological changes, and injury and apoptosis in the nervous cells in brain were assessed. The expression of miR-26a and CTGF in SHED and rats' brain tissues was evaluated and the target relation between miR-26a and CTGF was detected.
In SHED after induction, upregulated miR-26a could increase number of dendritic spines, cell proliferation, and expression of β3 tubulin, MAP-2 and GFAP, and restrain CTGF expression. In rat models, SHED engineered to overexpress miR-26a could attenuate brain water content, Evans blue content, apoptosis, pathological injury and expression of CTGF and Bax, while promoted number of Nissl bodies and expression of Bcl-2 in the nervous cells in brain in ICH rats. Furthermore, miR-26a competitively bound to CTGF.
Our findings provided the evidence that SHED could transmit miR-26a to protect ICH rats from cerebral injury by repressing CTGF, which may contribute to ICH therapy.
大量研究表明，人脱落乳牙干细胞（SHED）对脑损伤具有保护作用，但具体机制尚不清楚。本研究聚焦于 SHED 传递的 microRNA（miR）-26a 在脑出血（ICH）中的作用。
从健康儿童的乳牙中提取 SHED，通过转染改变 SHED 中 miR-26a 的表达，然后对 SHED 进行神经元分化诱导，检测β3 微管蛋白、MAP-2 和胶质纤维酸性蛋白（GFAP）的表达、树突棘数量和细胞增殖。通过立体定向注射 VII 型胶原酶到左侧纹状体建立 ICH 大鼠模型，并用 miR-26a 模拟物或抑制剂转染的 SHED 悬浮液注射建模大鼠。然后评估脑水含量、血脑屏障通透性、脑组织病理变化以及损伤和细胞凋亡。评估 SHED 和大鼠脑组织中 miR-26a 和 CTGF 的表达，并检测 miR-26a 与 CTGF 的靶关系。
在诱导后的 SHED 中，上调的 miR-26a 可以增加树突棘数量、细胞增殖以及β3 微管蛋白、MAP-2 和 GFAP 的表达，并抑制 CTGF 的表达。在大鼠模型中，过表达 miR-26a 的 SHED 可以减轻 ICH 大鼠的脑含水量、伊文思蓝含量、凋亡、病理损伤和 CTGF、Bax 的表达，同时促进 Nissl 体数量和 Bcl-2 的表达在 ICH 大鼠的神经细胞中。此外，miR-26a 与 CTGF 竞争结合。
我们的研究结果提供了证据表明，SHED 可以通过抑制 CTGF 向 ICH 大鼠传递 miR-26a 来保护其免受脑损伤，这可能有助于 ICH 的治疗。
