Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway.
Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway.
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DOI：
10.1038/s41598-022-09882-7
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发表时间：
2022-04-07
影响因子：
4.6
通讯作者：
Koibuchi N
中科院分区：
文献类型：
--
作者：
Ariyani W;Miyazaki W;Tsushima Y;Koibuchi N
基于Gd(Gd)的造影剂(GBCA)是在磁共振成像期间静脉注射的化学物质，以提高诊断效率。反复使用GBCA会导致它们在大脑中沉积。这种沉积可能会影响到各种神经细胞，包括星形胶质细胞。在这项研究中，我们研究了GBCA(Omniscan、Magnescope、Magnevist和Gadovist)对星形胶质细胞迁移的影响，这对发育过程中神经元的形成和维持脑内环境稳定至关重要。所有的GBCA都通过增加肌动蛋白的重塑来增加细胞的迁移和黏附。整合素αvβ3被RNA干扰或暴露于整合素αvβ3抑制剂可减少星形胶质细胞的迁移。GBCA使α-v-β-3下游因子FAK、ERK1/2和Akt的磷酸化水平升高。RNA干扰或整合素αvβ3抑制剂均可使上述因子的磷酸化水平降低。GBCA还增加了属于RhoGTP酶家族的下游因子rac1/CDc42的磷酸化。共同暴露于选择性RhoGTP酶抑制剂，降低了GBCA对细胞迁移的影响。这些发现表明，GBCA通过整合素αvβ3发挥作用，激活信号通路，导致星形胶质细胞迁移增加。因此，研究结果表明，重要的是要避免重复使用GBCA，以防止对大脑的不良副作用，特别是在发育期间。
Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging to enhance the diagnostic yield. Repeated use of GBCAs causes their deposition in the brain. Such deposition may affect various neuronal cells, including astrocytes. In this study, we examined the effect of GBCAs (Omniscan, Magnescope, Magnevist, and Gadovist) on astrocyte migration, which is critical for formation of neurons during development and maintaining brain homeostasis. All GBCAs increased cell migration and adhesion with increased actin remodelling. Knockdown of integrin αvβ3 by RNAi or exposure to integrin αvβ3 inhibitor reduced astrocyte migration. GBCAs increased phosphorylation of downstream factors of αvβ3, such as FAK, ERK1/2, and Akt. The phosphorylation of all these factors were reduced by RNAi or integrin αvβ3 inhibitor. GBCAs also increased the phosphorylation of their downstream factor, Rac1/cdc42, belonging to the RhoGTPases family. Coexposure to the selective RhoGTPases inhibitors, decreased the effects of GBCAs on cell migration. These findings indicate that GBCAs exert their action via integrin αvβ3 to activate the signaling pathway, resulting in increased astrocyte migration. Thus, the findings of the study suggest that it is important to avoid the repeated use of GBCAs to prevent adverse side effects in the brain, particularly during development.
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影响因子：
5.2
作者：
Ariyani W;Iwasaki T;Miyazaki W;Khongorzul E;Nakajima T;Kameo S;Koyama H;Tsushima Y;Koibuchi N
通讯作者：
Koibuchi N
影响因子：
19.7
作者：
Gianolio, Eliana;Bardini, Paola;Aime, Silvio
通讯作者：
Aime, Silvio
影响因子：
4.7
作者：
Hsu, Hsiang-Hao;Hoffmann, Sigrid;Pavenstaedt, Hermann
通讯作者：
Pavenstaedt, Hermann
钆通过促进细胞外 Ca2+ 的流入，触发原代培养的大鼠皮质星形胶质细胞中的未折叠蛋白反应 (UPR)
影响因子：
6.1
作者：
Feng, Xu-Dong;Xia, Qing;Wang, Kui
通讯作者：
Wang, Kui
星形胶质细胞功能和神经回路中表型的多样性。
影响因子：
25
作者：
Khakh BS;Sofroniew MV
通讯作者：
Sofroniew MV