WKYMVm/FPR2 Alleviates Spinal Cord Injury by Attenuating the Inflammatory Response of Microglia.
WKYMVm/FPR2 Alleviates Spinal Cord Injury by Attenuating the Inflammatory Response of Microglia.
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DOI：
10.1155/2022/4408099
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发表时间：
2022
影响因子：
4.6
通讯作者：
Li, Xiang
中科院分区：
文献类型：
--
作者：
Zhang, Wenwu;Chen, Jiewen;Guo, Weimin;Kong, Ganggang;Wang, Le;Cheng, Xing;Zeng, Xiaolin;Wan, Yong;Li, Xiang
脊髓损伤是一种常见的神经系统外伤性疾病。脊髓损伤的病理生理过程包括原发性损伤和继发性损伤。过度的炎症反应导致继发性组织损伤，进而加剧细胞和器官功能障碍。由于原发性损伤的不可逆性，目前对脊髓损伤的研究主要集中在继发性损伤上，炎症反应被认为是主要的目标。因此，调节炎症反应被认为是治疗脊髓损伤的一种新策略。本研究采用小胶质细胞系、原代小胶质细胞和脊髓损伤大鼠模型，发现WKYMVm/FPR2通过抑制细胞外信号调节激酶1和2 （ERK1/2）和核因子-κB （NF-κB）信号通路发挥抗炎作用，减轻脊髓损伤后的组织损伤。FPR2被WKYMVm激活，通过抑制M1小胶质细胞极化抑制肿瘤坏死因子-α (TNF-α)、白细胞介素-6 （IL-6）、白细胞介素-1β (IL-1β)的分泌。此外，WKYMVm激活FPR2可以减少脊髓损伤大鼠的结构障碍和神经元丢失。综上所述，本研究表明WKYMVm激活FPR2通过抑制ERK1/2和NF-κB信号通路抑制M1小胶质细胞极化，从而减轻脊髓损伤后的组织损伤和运动能力下降。这些发现提供了对脊髓损伤的进一步了解，并有助于确定新的治疗策略。
Spinal cord injury (SCI) is a common traumatic disease of the nervous system. The pathophysiological process of SCI includes primary injury and secondary injuries. An excessive inflammatory response leads to secondary tissue damage, which in turn exacerbates cellular and organ dysfunction. Due to the irreversibility of primary injury, current research on SCI mainly focuses on secondary injury, and the inflammatory response is considered the primary target. Thus, modulating the inflammatory response has been suggested as a new strategy for the treatment of SCI. In this study, microglial cell lines, primary microglia, and a rat SCI model were used, and we found that WKYMVm/FPR2 plays an anti-inflammatory role and reduces tissue damage after SCI by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways. FPR2 was activated by WKYMVm, suppressing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by inhibiting M1 microglial polarization. Moreover, FPR2 activation by WKYMVm could reduce structural disorders and neuronal loss in SCI rats. Overall, this study illustrated that the activation of FPR2 by WKYMVm repressed M1 microglial polarization by suppressing the ERK1/2 and NF-κB signaling pathways to alleviate tissue damage and locomotor decline after SCI. These findings provide further insight into SCI and help identify novel treatment strategies.
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影响因子：
--
作者：
Goldmann T;Prinz M
通讯作者：
Prinz M
影响因子：
9.3
作者：
Hellenbrand DJ;Quinn CM;Piper ZJ;Morehouse CN;Fixel JA;Hanna AS
通讯作者：
Hanna AS
影响因子：
5.6
作者：
Jun JH;Park SY;Park S;Park HJ;Kim JY;Park GT;Bae SH;Kim JH;Kim GJ
通讯作者：
Kim GJ
影响因子：
4.4
作者：
Kim, Sang Doo;Kim, Yoon-Keun;Bae, Yoe-Sik
通讯作者：
Bae, Yoe-Sik
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG