Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway
Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway
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DOI：
10.1007/s12264-023-01128-4
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发表时间：
2023-10-21
影响因子：
5.6
通讯作者：
Deng，David Y. B.
中科院分区：
文献类型：
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作者：
Xia，Yu;Ding，Lu;Deng，David Y. B.
脊髓损伤（SCI）是最具破坏性的创伤之一，星形胶质细胞的异常增殖通常会导致神经功能缺损。然而，SCI后星形胶质细胞过度增殖的机制尚不清楚。Grin 2c（谷氨酸离子型受体2c）在细胞增殖中起重要作用。我们的生物信息学分析表明，Grin 2c和Ca 2+转运功能在SCI后星形胶质细胞受到抑制。Grin 2c通过抑制钙/钙调蛋白依赖性蛋白激酶2b（CaMK 2b）途径促进星形胶质细胞增殖。通过筛选不同的炎症因子，进一步发现白细胞介素1α（IL 1 α）抑制Grin 2c/Ca 2 +/CaMK 2b，并在氧化损伤模型中促进星形胶质细胞增殖。使用中和抗体阻断IL 1 α导致SCI后Grin 2c表达增加和星形胶质细胞增殖抑制。总之，本研究提示IL 1 α通过抑制SCI后Grin 2c/Ca 2 +/CaMK 2b通路促进星形胶质细胞增殖，揭示了星形胶质细胞增殖的一种新的病理机制，可能为SCI修复提供潜在的靶点。
Spinal cord injury (SCI) is one of the most devastating traumas, and the aberrant proliferation of astrocytes usually causes neurological deficits. However, the mechanism underlying astrocyte over-proliferation after SCI is unclear. Grin2c (glutamate ionotropic receptor type 2c) plays an essential role in cell proliferation. Our bioinformatic analysis indicated that Grin2c and Ca2+transport functions were inhibited in astrocytes after SCI. Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca2+/calmodulin-dependent protein kinase 2b (CaMK2b) pathwayin vitro. By screening different inflammatory factors, interleukin 1α (IL1α) was further found to inhibit Grin2c/Ca2+/CaMK2b and enhance astrocyte proliferation in an oxidative damage model. Blockade of IL1α using neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI. Overall, this study suggests that IL1α promotes astrocyte proliferation by suppressing the Grin2c/Ca2+/CaMK2b pathway after SCI, revealing a novel pathological mechanism of astrocyte proliferation, and may provide potential targets for SCI repair.