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Suppression of TGFβR‑Smad3 pathway alleviates the syrinx induced by syringomyelia

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机构: [1]Department of Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital Capital Medical University, 45 Changchun Street, Beijing 100053, China [2]Cell Therapy Center, Xuanwu Hospital Capital Medical University, 45 Changchun Street, Beijing 100053, China [3]Spine Center, China International Neuroscience Institute (CHINA-INI), Beijing, China [4]Lab of Spinal Cord Injury and Functional Reconstruction, Xuanwu Hospital, Capital Medical University, Beijing, China [5]Research Center of Spine and Spinal Cord, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China [6]National Center for Neurological Disorders, Beijing, China.
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关键词: Spinal cord Central canal Ependymal cells Syrinx

摘要:
Syringomyelia is a cerebrospinal fluid (CSF) disorder resulted in separation of pain and temperature, dilation of central canal and formation of syrinx in central canal. It is unclear about mechanisms of the dilation and syrinx formation. We aimed to investigate roles of ependymal cells lining central canal on the dilation, trying to reduce syrinx formation in central canal.We employed 78 Sprague-Dawley (SD) rats totally with syringomyelia to detect the contribution of ependymal cells to the dilation of central canal. Immunofluorescence was used to examine the activation of ependymal cells in 54 syringomyelia rat models. BrdU was used to indicate the proliferation of ependymal cells through intraperitoneal administration in 6 syringomyelia rat models. 18 rats with syringomyelia were injected with SIS3, an inhibitor of TGFβR-Smad3, and rats injected with DMSO  were used as control. Among the 18 rats, 12 rats were used for observation of syrinx following SIS3 or DMSO administration by using magnetic resonance imaging (MRI) on day 14 and day 30 under syringomyelia without decompression. All the data were expressed as mean ± standard deviation (mean ± SD). Differences between groups were compared using the two-tailed Student's t-test or ANOVA. Differences were considered significant when *p < 0.05.Our study showed the dilation and protrusions of central canal on day 5 and enlargement from day 14 after syringomyelia induction in rats with activation of ependymal cells lining central canal. Moreover, the ependymal cells contributed to protrusion formation possibly through migration along with central canal. Furthermore, suppression of TGFβR-Smad3 which was crucial for migration reversed the size of syrnix in central canal without treatment of decompression, suggesting TGFβR-Smad3 signal might be key for dilation of central canal and formation of syrinx.The size of syrinx was decreased after SIS3 administration without decompression. Our study depicted the mechanisms of syrinx formation and suggested TGFβR-Smad3 signal might be key for dilation of central canal and formation of syrinx.© 2023. The Author(s).

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
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出版当年[2021]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Department of Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital Capital Medical University, 45 Changchun Street, Beijing 100053, China [2]Cell Therapy Center, Xuanwu Hospital Capital Medical University, 45 Changchun Street, Beijing 100053, China
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通讯作者:
通讯机构: [1]Department of Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital Capital Medical University, 45 Changchun Street, Beijing 100053, China [3]Spine Center, China International Neuroscience Institute (CHINA-INI), Beijing, China [4]Lab of Spinal Cord Injury and Functional Reconstruction, Xuanwu Hospital, Capital Medical University, Beijing, China [5]Research Center of Spine and Spinal Cord, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China [6]National Center for Neurological Disorders, Beijing, China.
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