机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China[2]The Central Laboratory Shenzhen Second People’s Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, China
Thrombolysis with tissue plasminogen activator (tPA) increases matrix metalloproteinase-9 (MMP-9) activity in the ischemic brain, which exacerbates blood-brain barrier injury and increases the risk of symptomatic cerebral hemorrhage. The mechanism through which tPA enhances MMP-9 activity is not well understood. Here we report an important role of caveolin-1 in mediating tPA-induced MMP-9 synthesis. Brain microvascular endothelial cell line bEnd3 cells were incubated with 5 or 20 lg/ml tPA for 24 hrs before analyzing MMP-9 levels in the conditioned media and cellular extracts by gelatin zymography. tPA at a dose of 20 lg/mL tPA, but not 5 lg/mL, significantly increased MMP-9 level in cultured media while decreasing it in cellular extracts. Concurrently, tPA treatment induced a 2.3-fold increase of caveolin-1 protein levels in endothelial cells. Interestingly, knockdown of Cav-1 with siRNA inhibited tPAinduced MMP-9 mRNA up-regulation and MMP-9 increase in the conditioned media, but did not affect MMP-9 decrease in cellular extracts. These results suggest that caveolin-1 critically contributes to tPA-mediated MMP-9 up-regulation, but may not facilitate MMP-9 secretion in endothelial cells.
基金：
This work was supported by Soochow University Research Startup
Fund to XJ (Q 421500113), the Priority Academic Program
Development of Jiangsu Higher Education Institutions of China to
XJ, and Shenzhen Science and Technology Innovation Commission
Research Grants to WL (CXZZ20130516152706040 and
ZDSY20140509173142601).
第一作者机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China[*1]Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
共同第一作者：
通讯作者：
通讯机构：[2]The Central Laboratory Shenzhen Second People’s Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, China[*1]Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
推荐引用方式(GB/T 7714)：
Jin Xinchun,Sun Yanyun,Xu Ji,et al.Caveolin-1 mediates tissue plasminogen activator-induced MMP-9 up-regulation in cultured brain microvascular endothelial cells[J].JOURNAL OF NEUROCHEMISTRY.2015,132(6):724-30.doi:10.1111/jnc.13065.
APA：
Jin, Xinchun,Sun, Yanyun,Xu, Ji&Liu, Wenlan.(2015).Caveolin-1 mediates tissue plasminogen activator-induced MMP-9 up-regulation in cultured brain microvascular endothelial cells.JOURNAL OF NEUROCHEMISTRY,132,(6)
MLA：
Jin, Xinchun,et al."Caveolin-1 mediates tissue plasminogen activator-induced MMP-9 up-regulation in cultured brain microvascular endothelial cells".JOURNAL OF NEUROCHEMISTRY 132..6(2015):724-30
医学