Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
J Mol Histol. 2012 Oct;43(5):543-52. doi: 10.1007/s10735-012-9431-1. Epub 2012 Jul 14.
Previous studies have suggested that bone morphogenetic protein-6 (BMP-6) has a pronounced upregulation in rat brains subjected to traumatic brain injury. Bone morphogenetic protein-10 (BMP-10) is a newly identified cardiac-specific peptide growth factor that belongs to the TGF-β superfamily. To elucidate the dynamic expression changes and cellular localization of BMP-10 during traumatic brain injury (TBI), we performed an acute traumatic brain injury model in adult rats. Western blot analysis, immunohistochemistry and RTPCR revealed that BMP-10 expression in impaired cerebral cortex was more strongly induced not only at protein level but also at mRNA level compared to that in normal group. Double immunofluorescence labeling suggested that BMP-10 was localized mainly in the cytoplasm of neurons, microglias, and astrocytes within 3 mm from the lesion site at day 3 post-injury. And there was a specific upregulation of BMP-10 in astrocytes following brain injury. Besides, co-localization of BMP-10 and proliferating cell nuclear antigen (PCNA) was detected in Glial fibrillary acidic protein (GFAP) (+) cells. We also examined the expression profiles of PCNA and GFAP whose change was correlated with the expression profiles of BMP-10 in the incised injury model used here. Another experiment in which astrocytes were treated with BMP-10 was also performed to confirm the relationship between the upregulation of BMP-10 and proliferation of astrocytes following TBI. Taken together, this is the first description of BMP-10 expression during the central nervous system (CNS) lesion and repair. Thus, the present data suggested that BMP-10 may be implicated in CNS pathophysiology after TBI. But, further studies are needed to understand the cell signal pathway which can direct the exact role of BMP-10 following traumatic brain injury.
先前的研究表明，骨形态发生蛋白-6（BMP-6）在创伤性脑损伤大鼠的大脑中表达明显上调。骨形态发生蛋白-10（BMP-10）是一种新发现的心脏特异性肽生长因子，属于 TGF-β超家族。为了阐明创伤性脑损伤（TBI）过程中 BMP-10 的动态表达变化和细胞定位，我们在成年大鼠中建立了急性创伤性脑损伤模型。Western blot 分析、免疫组织化学和 RT-PCR 显示，与正常组相比，损伤大脑皮质中 BMP-10 的表达不仅在蛋白质水平上，而且在 mRNA 水平上都更强地诱导。双免疫荧光标记表明，BMP-10 主要定位于损伤部位 3mm 内神经元、小胶质细胞和星形胶质细胞的细胞质中。脑损伤后星形胶质细胞中 BMP-10 特异性上调。此外，还检测到 BMP-10 与增殖细胞核抗原（PCNA）在胶质纤维酸性蛋白（GFAP）（+）细胞中的共定位。我们还检查了 PCNA 和 GFAP 的表达谱，其变化与这里使用的切口损伤模型中 BMP-10 的表达谱相关。还进行了另一个用 BMP-10 处理星形胶质细胞的实验，以确认 TBI 后 BMP-10 上调与星形胶质细胞增殖之间的关系。综上所述，这是首次描述 BMP-10 在中枢神经系统（CNS）损伤和修复过程中的表达。因此，目前的数据表明，BMP-10 可能参与 TBI 后的中枢神经系统病理生理学。但是，需要进一步的研究来了解可以指导 TBI 后 BMP-10 确切作用的细胞信号通路。
