Role of bone morphogenetic protein-2/4 in astrocyte activation in neuropathic pain
Role of bone morphogenetic protein-2/4 in astrocyte activation in neuropathic pain
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骨形态发生蛋白-2/4 在神经性疼痛星形胶质细胞激活中的作用
DOI：
10.1177/1744806919892100
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发表时间：
2019-01
期刊：
影响因子：
3.3
通讯作者：
Wang Yaping
中科院分区：
文献类型：
--
作者：
Yang Lin;Liu Shuxin;Wang Yaping
骨形态发生蛋白2/4（Bone morphogenetic protein-2/4，BMP 2/4）被认为是星形胶质细胞活性的促进剂。大量证据表明，BMP 2/4可能升高，并在脊髓损伤后星形胶质细胞活化中起关键作用。虽然神经性疼痛与星形胶质细胞活化类似，但BMP 2/4在这方面的参与仍不清楚。方法采用L5脊神经结扎法建立大鼠神经病理性疼痛模型，观察大鼠脊髓胶质细胞酸性蛋白和骨形态发生蛋白2/4在第1、4、7、10、14天的表达。接下来，正常大鼠接受鞘内外源性BMP 2/4和拮抗剂Noggin以评估BMP 2/4对星形胶质细胞活化的影响。在两个实验中，使用von Frey细丝来评价缩爪阈值的变化。采用免疫印迹法和免疫荧光法检测脊髓胶质细胞酸性蛋白、BMP 2/4、p-Smad 1/5/8和磷酸化信号转导子和转录激活子3（p-STAT 3）的表达。结果1.脊神经结扎后，大鼠脊髓组织中BMP 4的表达明显增加，而BMP 2的表达无明显变化。第二，外源性BMP 4而非BMP 2诱导缩足阈值显著降低，沿着胶质细胞酸性蛋白的上调。此外，外源性BMP 4刺激p-Smad 1/5/8和p-STAT 3，而BMP 2仅上调p-Smad 1/5/8。最后，外源性Noggin减轻了由BMP 4诱导的缩爪阈值的降低，并减少了星形胶质细胞活化以及p-STAT 3上调。结论大鼠痛觉超敏反应中只有BMP 4参与，而BMP 2不参与，可能通过p-Smad 1/5/8和p-STAT 3信号通路激活胶质细胞。
Background Bone morphogenetic protein-2/4 (BMP2/4) has been recognized as promoters of astrocyte activity. Substantial evidence suggests that BMP2/4 may be elevated and plays a critical role in astrocyte activation upon spinal cord injury. Although neuropathic pain is similarly associated with astrocyte activation, the participation of BMP2/4 in this regard still remains unclear. Methods A rat model of neuropathic pain achieved by spinal nerve ligation at L5 was used to evaluate the expression of glial fibrillary acidic protein and BMP2/4 in the spinal cord in days 1, 4, 7, 10, and 14. Next, normal rats received intrathecal exogenous BMP2/4 and the antagonist Noggin to assess the effect of BMP2/4 on astrocyte activation. In both experiments, von Frey filaments were used to evaluate the changes in paw withdrawal threshold. In addition, Western blotting and immunofluorescence were performed to assess the expression of glial fibrillary acidic protein, BMP2/4, p-Smad 1/5/8, and phospho-signal transducer and activator of transcription-3 (p-STAT3) in the spinal cord. Results Firstly, spinal nerve ligation caused a significant increase in the expression of BMP4, while BMP2 levels remained unchanged. Secondly, exogenous BMP4 but not BMP2 induced a significant decrease in paw withdrawal threshold, along with the upregulation of glial fibrillary acidic protein. Moreover, exogenous BMP4 stimulated both p-Smad 1/5/8 and p-STAT3, while BMP2 only upregulated p-Smad 1/5/8. Finally, exogenous Noggin alleviated the decrease in paw withdrawal threshold induced by BMP4 and reduced astrocyte activation, as well as p-STAT3 upregulation. Conclusions Our results indicate only BMP4—and not BMP2—intervened in allodynia in rats by eliciting glial activation probably through both p-Smad 1/5/8 and p-STAT3 signaling.
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影响因子：
2.4
作者：
Mitchell K;Shah JP;Dalgard CL;Tsytsikova LV;Tipton AC;Dmitriev AE;Symes AJ
通讯作者：
Symes AJ
DOI：
10.1523/jneurosci.5524-09.2011
发表时间：
2011-04-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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影响因子：
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作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
1.4
作者：
Jian-Guo Hu;Yu-Xin Zhang;Q. Qi;Rui Wang;Lin Shen;Chen Zhang;Jin Xi;Jian-sheng Zhou;He-zuo Lu
通讯作者：
Jian-Guo Hu;Yu-Xin Zhang;Q. Qi;Rui Wang;Lin Shen;Chen Zhang;Jin Xi;Jian-sheng Zhou;He-zuo Lu