TNFR2 knockdown triggers apoptosis-induced proliferation in primarily cultured Schwann cells
TNFR2 knockdown triggers apoptosis-induced proliferation in primarily cultured Schwann cells
复制标题
TNFR2 敲低会触发原代培养的雪旺细胞中凋亡诱导的增殖。
DOI：
10.1016/j.neures.2019.01.010
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发表时间：
2020-01-01
影响因子：
2.9
通讯作者：
Zhou, Songlin
中科院分区：
文献类型：
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作者：
Gao, Zhongyang;Min, Cuiting;Zhou, Songlin
坐骨神经损伤后，损伤远端段的雪旺细胞在凋亡的同时也发生增殖。虽然细胞凋亡诱导的增殖（AiP）已在各种模型中的特点，是否在远端节段的雪旺细胞的增殖是由细胞凋亡触发仍然没有阐明。本研究利用小干扰RNA（siRNA）分别下调原代培养的雪旺细胞中TNFR 1和TNFR 2的表达，观察其对雪旺细胞凋亡和增殖的影响。TNFR 1或TNFR 2的下调导致雪旺细胞的存活率显著降低，并显著增加雪旺细胞的凋亡。与此相反，TNFR 2的敲低诱导的细胞凋亡，而不是TNFR 1，促进雪旺细胞增殖。总之，这些观察结果表明，许旺细胞可以经历AiP，TNFR 2敲低触发了这一过程。此外，我们建立了TNF-α基因敲除（KO）小鼠坐骨神经损伤模型，发现KO小鼠远段雪旺细胞凋亡和增殖明显少于野生型小鼠，提示TNF-α及其受体在坐骨神经损伤后雪旺细胞大量凋亡和凋亡诱导的增殖中起重要作用。雪旺细胞中AiP的发现可能有助于开发新的促进轴突再生的方法，从而促进周围神经损伤后的功能恢复。(C)2019 Elsevier B. V.和日本神经科学学会。All rights reserved.
After sciatic nerve injury, Schwann cells in the distal segments of injury site undergo apoptosis and meanwhile proliferation. Although apoptosis-induced proliferation (AiP) has been characterized in various models, whether the proliferation of Schwann cells in the distal segments is triggered by apoptosis remains unelucidated. In this study, we used small interfering RNA to knock down the expression of TNFR1 and TNFR2 in primarily cultured Schwann cells, respectively and observed its effects on apoptosis and proliferation. The downregulation of TNFR1 or TNFR2 resulted in a remarkable decrease of cell viability and dramatically increased the apoptosis of Schwann cells. In contrast, the cell apoptosis induced by the knockdown of TNFR2, but not TNFR1, promoted the Schwann cell proliferation. Together, these observations indicated that Schwann cells can undergo AiP, and TNFR2 knockdown triggers the process. Additionally, we established the sciatic nerve injury model on TNF-alpha knock-out (KO) mice, and found that the Schwann cells of KO mice occurred significantly less apoptosis and proliferation than that of wild-type mice in the distal segments, which indicated TNF-alpha and its receptors were essential in the massive apoptosis and the apoptosis-induced proliferation of Schwann cells after sciatic nerve injury. The finding of AiP in Schwann cells may be beneficial to develop new approaches to promote axon regeneration and thereby improve the functional recovery after peripheral nerve injury. (C) 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.