Chloride Intracellular Channel Protein 2 Promotes Microglial Invasion: A Link to Microgliosis in the Parkinson's Disease Brain.
Chloride Intracellular Channel Protein 2 Promotes Microglial Invasion: A Link to Microgliosis in the Parkinson's Disease Brain.
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DOI：
10.3390/brainsci13010055
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发表时间：
2022-12-28
期刊：
影响因子：
3.3
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Choudhury, Mohammed E.;Ozaki, Saya;Miyaue, Noriyuki;Matsuura, Taisei;Mikami, Kanta;Islam, Afsana;Kubo, Madoka;Ando, Rina;Yano, Hajime;Kunieda, Takeharu;Nagai, Masahiro;Tanaka, Junya
激活的小胶质细胞可能导致帕金森病（PD）的神经退行性变。基质金属蛋白酶（Matrix metalloproteinase， MMP）-9在帕金森病的发病机制中起着至关重要的作用，但MMP-9在小胶质细胞释放中的调节作用尚不清楚。鉴于氯离子胞内通道蛋白2 （CLIC2）对mmmp的调节作用，我们旨在确定CLIC2在调节小胶质细胞MMP表达和激活中的作用。我们发现CLIC2在大鼠脑组织的小胶质细胞和神经元中表达，并重点研究了CLIC2在原代培养的小胶质细胞中的功能。暴露于重组CLIC2蛋白增强了小胶质细胞侵袭活性，而其敲低则消除了这种活性。此外，通过添加CLIC2蛋白证实了MMP-9的激活增加，而CLIC2敲除消除了这种激活。此外，pd模型组织中CLIC2表达增加。总之，CLIC2增加了参与PD发病的小胶质细胞中MMP-9的活性。
Activated microglia potentially cause neurodegeneration in Parkinson’s disease (PD). Matrix metalloproteinase (MMP)-9 plays a crucial role in the pathogenesis of PD, but the modulator of microglial release of MMP-9 remains obscure. Given the modulatory effect of chloride intracellular channel protein 2 (CLIC2) on MMPs, we aimed to determine the role of CLIC2 in regulating microglial MMP expression and activation. We found that CLIC2 is expressed in microglia and neurons in rat brain tissue and focused on the function of CLIC2 in primary cultured microglia. Exposure to recombinant CLIC2 protein enhanced microglial invasion activity, and its knockdown abolished this activity. Moreover, increased activation of MMP-9 was confirmed by the addition of the CLIC2 protein, and CLIC2 knockdown eliminated this activation. Additionally, increased expression of CLIC2 was observed in PD-modeled tissue. In conclusion, CLIC2 increases MMP-9 activity in the microglia, which are involved in PD pathogenesis.
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DOI：
10.1016/j.neo.2021.06.001
发表时间：
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期刊：
Neoplasia (New York, N.Y.)
影响因子：
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影响因子：
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作者：
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DOI：
10.1111/acer.14754
发表时间：
2022-01
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bogenpohl JW;Weston RM;Foreman TN;Kitchen KE;Miles MF
通讯作者：
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