Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter
Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter
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DOI：
10.1007/s11064-023-03929-5
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发表时间：
2023-04
影响因子：
4.4
通讯作者：
E. Furube;Masahiro Ohgidani;S. Yoshida
中科院分区：
文献类型：
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作者：
E. Furube;Masahiro Ohgidani;S. Yoshida
轴突损伤和脱髓鞘发生在脱髓鞘疾病中，例如多发性硬化症，并且髓鞘从轴突的脱离先于其降解。副阳极是每层髓鞘与轴突紧密粘附的区域。炎症过程中结和结旁结构的破坏是各种神经系统疾病的重要病理生理学。然而，这些结构的潜在病理变化仍不清楚。激肽释放酶6（KLK 6）是一种由少突胶质细胞产生的丝氨酸蛋白酶，参与脱髓鞘疾病。在本研究中，我们腹腔注射LPS小鼠数天，并检查KLK 6的定位变化。在LPS诱导的全身炎症过程中，观察到KLK 6在脊髓中的旁阳极细胞内定位的瞬时变化。但在脑白色物质的上部未检测到这些变化。LPS诱导的变化被米诺环素抑制，表明小胶质细胞的参与。此外，淋巴结长度在LPS处理的野生型小鼠中延长，但在LPS处理的KLK 6-KO小鼠中没有延长。这些结果证明了KLK 6在脱髓鞘过程中的潜在参与。
Axonal injury and demyelination occur in demyelinating diseases, such as multiple sclerosis, and the detachment of myelin from axons precedes its degradation. Paranodes are the areas at which each layer of the myelin sheath adheres tightly to axons. The destruction of nodal and paranodal structures during inflammation is an important pathophysiology of various neurological disorders. However, the underlying pathological changes in these structures remain unclear. Kallikrein 6 (KLK6), a serine protease produced by oligodendrocytes, is involved in demyelinating diseases. In the present study, we intraperitoneally injected mice with LPS for several days and examined changes in the localization of KLK6. Transient changes in the intracellular localization of KLK6 to paranodes in the spinal cord were observed during LPS-induced systemic inflammation. However, these changes were not detected in the upper part of brain white matter. LPS-induced changes were suppressed by minocycline, suggesting the involvement of microglia. Moreover, nodal lengths were elongated in LPS-treated wild-type mice, but not in LPS-treated KLK6-KO mice. These results demonstrate the potential involvement of KLK6 in the process of demyelination.