Different modifications of phosphorylated Smad3C and Smad3L through TGF-β after spinal cord injury in mice
Different modifications of phosphorylated Smad3C and Smad3L through TGF-β after spinal cord injury in mice
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DOI：
10.1016/j.neulet.2013.05.042
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发表时间：
2013-08-09
影响因子：
2.5
通讯作者：
Takayasu, Masakazu
中科院分区：
文献类型：
--
作者：
Joko, Masahiro;Osuka, Koji;Takayasu, Masakazu
转化生长因子-β（TGF-β）是一种抗炎细胞因子，在受损的脊髓中表达。TGF-β通过受体发出信号激活Smad蛋白，Smad蛋白易位到细胞核中。在本研究中，我们调查了小鼠脊髓损伤（SCI）后TGF-β/Smad信号通路的时间变化和细胞定位。ELISA分析显示，损伤脊髓中白细胞介素-6（IL-6）的浓度在SCI后立即显著升高，而TGF-β的浓度在SCI后逐渐升高，在2d达到峰值，然后逐渐降低。免疫组化结果显示Smad 3主要表达于脊髓神经元。在前角的运动神经元内染色的C-末端磷酸化Smad 3（p-Smad 3C），而在灰质内的星形胶质细胞中表达的连接区磷酸化Smad 3（p-Smad 3L）。这些发现表明SCI诱导TGF-β逐渐增加，并诱导p-Smad 3C和p-Smad 3L的不同激活。磷酸化Smad 3C可能参与了脊髓损伤后神经元的变性，而p-Smad 3L可能在星形胶质细胞形成胶质瘢痕中发挥作用。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Transforming growth factor-beta (TGF-beta) is an anti-inflammatory cytokine and is expressed in the injured spinal cord. TGF-beta signals through receptors to activate Smad proteins, which translocate into the nucleus. In the present study, we investigated the chronological alterations and cellular locations of the TGF-beta/Smad signaling pathway following spinal cord injury (SCI) in mice. ELISA analysis showed that the concentration of interleukin-6 (IL-6) in injured spinal cords significantly increases immediately after SCI, while the concentration of TGF-beta gradually increased after SCI, peaked at 2 days, and then gradually decreased. Immunohistochemical studies revealed that Smad3 was mainly expressed in neurons of the spinal cord. Phosphorylated Smad3 at the C-terminus (p-Smad3C) was stained within the motor neurons in the anterior horn, while phosphorylated Smad3 at the linker regions (p-Smad3L) was expressed in astrocytes within gray matter. These findings suggest that SCI induces gradual increases in TGF-beta and induces different activation of p-Smad3C and p-Smad3L. Phosphorylated Smad3C might be involved in neuronal degeneration after SCI, and p-Smad3L may play a role in glial scar formation by astrocytes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.