CLEC5A Promotes Neuronal Pyroptosis in Rat Spinal Cord Injury Models by Interacting with TREM1 and Elevating NLRC4 Expression

被引：0

作者：

Tan, Yonghong ^{[1
]}

Wang, Qiong ^{[1
]}

Guo, Yubing ^{[1
]}

Zhang, Na ^{[1
]}

Xu, Yingyi ^{[1
]}

Bai, Xue ^{[1
]}

Liu, Jianhua ^{[1
]}

Bi, Xiaobao ^{[1
]}

机构：

[1] Guangdong Prov Clin Res Ctr Child Hlth, Guangzhou Women & Childrens Med Ctr, Dept Anesthesiol, Guangzhou 510623, Peoples R China

来源：

ENEURO | 2024年 / 11卷 / 10期

关键词：

CLEC5A; NLRC4; neuronal pyroptosis; spinal cord injury; TREM1; OXIDATIVE STRESS;

D O I：

10.1523/ENEURO.0111-24.2024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Pyroptosis, an inflammatory programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of pyroptosis-related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1 beta levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1 beta in lidocaine-induced PC12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.

引用

页数：15