The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury.
The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury.
复制标题
整合素 α(v)β (8) 在新生儿缺氧缺血性脑损伤中的作用。
DOI：
10.1007/s12640-009-9117-y
复制
发表时间：
2010-05
影响因子：
3.7
通讯作者：
Mu, Dezhi
中科院分区：
文献类型：
--
作者：
Li, Jinhui;Qu, Yi;Li, Xihong;Li, Deyuan;Zhao, Fengyan;Mao, Meng;Ferriero, Donna;Mu, Dezhi
整合素αvβ8在脑血管发育中起重要作用。已证实αvβ8是上皮细胞转化生长因子β1（TGF-β1）活化的关键因子。但αvβ8是否能激活TGF-β1并在新生儿缺氧缺血性脑损伤中发挥保护作用尚不清楚。本研究探讨了αvβ8与TGF-β1活化的关系，以及TGF-β1活化在缺氧缺血（hypoxia-ischemia，HI）神经元保护中的作用。体外培养大鼠脑星形胶质细胞和神经元，采用氧糖剥夺建立缺氧缺血模型。采用免疫细胞化学、蛋白质印迹和逆转录聚合酶链反应测定β8表达。通过TGF-β生物测定法在受试细胞（星形胶质细胞）和报告细胞共培养系统中测定TGF-β1活化。Western blot检测促凋亡蛋白Caspase-3和抗凋亡蛋白Bcl-2、Bcl-xL的表达。TUNEL法检测细胞凋亡。结果发现，常氧条件下，β8在星形胶质细胞中的表达强于神经元。HI可导致星形胶质细胞β8表达迅速而持续的增加，而神经元仅轻微而短暂的增加。星形胶质细胞β8可诱导TGF-β1上调Bcl-2和Bcl-xL表达，从而减轻神经元凋亡。提示β8通过TGF-β1信号通路对新生儿HI脑损伤具有保护作用，这可能为HI脑损伤的治疗提供了新的思路。
Integrin αvβ8 plays an important role in cerebral vascular development. It has been proven that αvβ8 is a key factor for transforming growth factor-β1 (TGF-β1) activation in epithelial cells. However, it is not clear whether αvβ8 can activate TGF-β1 and play a role in protection during neonatal hypoxic-ischemic brain injury. In this study, we investigated the relationship between αvβ8 and TGF-β1 activation, and thus the effects of TGF-β1 activation in the protection of neurons after hypoxia-ischemia (HI). Astrocytes and neurons from rat brains were cultured and then subjected to oxygen–glucose deprivation to generate HI model in vitro. β8 expression was determined using immunocytochemistry, western blot, and reverse-transcriptase polymerase chain reaction. TGF-β1 activation was determined by TGF-β bioassay in a tested cell (astrocyte) and a reporter cell co-culture system. The pro-apoptotic protein, cleaved caspase-3, and the anti-apoptotic protein, Bcl-2 and Bcl-xL, were detected using western blot. Cellular apoptosis was detected with TUNEL. We found that β8 expression was stronger in astrocytes than that in neurons under normoxia. HI resulted in a rapid and persistent increase of β8 expression in astrocytes, but only in a slight and transient increase in neurons. Astrocytes β8 could induce TGF-β1 leading to upregulation of Bcl-2 and Bcl-xL, and thus attenuated neuronal apoptosis. The present findings suggest that β8 protecting the brain against neonatal HI injury through TGF-β1 signaling pathway, which may have implications for the treatment of HI brain injury.
登录
查看更多内容
DOI：
10.1097/01.wcb.0000090080.64176.44
发表时间：
2003-10-01
影响因子：
6.3
作者：
Boche, D;Cunningham, C;Perry, VH
通讯作者：
Perry, VH
影响因子：
4.8
作者：
Mishra, DP;Pal, R;Shaha, C
通讯作者：
Shaha, C
影响因子：
5.3
作者：
Proctor, JM;Zang, KL;Reichardt, LF
通讯作者：
Reichardt, LF
影响因子：
6.2
作者：
Fu, Xuemei;Li, Qiuping;Mu, Dezhi
通讯作者：
Mu, Dezhi
影响因子：
3.7
作者：
Schmuck, G.;Roehrdanz, E.;Schlueter, G.
通讯作者：
Schlueter, G.