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In Vitro Functional Study of YES-Associated Protein (YAP) in Murine Brain Endothelial Cells under Normal and Ischemic Conditions

Al-Waili, Daniah I
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037357

Abstract Details

2015, MS, University of Cincinnati, Pharmacy: Pharmaceutical Sciences.
The Hippo pathway is a highly conserved signaling pathway in mammals. It controls organ size and tissue homeostasis through a cascade of kinases that leads to deactivation of YES-Associated Protein (YAP), a key player in this pathway. YAP is a transcription co-activator that acts as an important growth promoter. YAP over expression has been linked to tumorigenesis in several tissue cancers. Also, YAP activity is thought to be important in cell apoptosis and chemotherapy resistance in certain cancers. Moreover, YAP role has been identified in early embryonic development as well as tissue regeneration later in life. Still, YAP in endothelial cells has not been extensively studied. Even though some studies showed its importance for endothelial proliferation and sprouting, the clear role and mechanism of YAP in endothelial cells is still poorly understood. In this research, we investigate the role of YAP in function of murine brain-derived endothelial cells (bEnd5) under both normal and ischemic condition by silencing YAP expression. Our study shows that reduction of Yap expression inhibits bEND5 cells proliferation, but has no effect on cell migration or adhesion molecules expression like ICAM-1 and VCAM-1 or cytoskeleton proteins like aß tubulin. Oxygen-glucose deprivation (OGD) reduces expression of YAP in bEnd5 cells, and knocking down Yap expression increases OGD-induced cell death in bEnd5 cells. Furthermore, the cell-cell contact inhibits YAP expression, while Yap is required for maintaining the integrity of the Blood-Brain barrier (BBB) in vitro. In conclusion, the present study indicates that YAP play important role in brain endothelial cell proliferation and modulating the function of brain endothelial cell and BBB. These findings give useful information for further understanding of neurodegenerative diseases and especially the ischemic stroke.
Jiukuan Hao, Ph.D. (Committee Chair)
Giovanni Pauletti, Ph.D. (Committee Member)
Yuhang Zhang, Ph.D. (Committee Member)
55 p.
Pharmaceuticals
ischemic stroke; blood-brain barrier; YAP; brain endothelial cells; tight junction proteins; cell proliferation

Recommended Citations

Citations

  • Al-Waili, D. I. (2015). In Vitro Functional Study of YES-Associated Protein (YAP) in Murine Brain Endothelial Cells under Normal and Ischemic Conditions [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037357

    APA Style (7th edition)

  • Al-Waili, Daniah. In Vitro Functional Study of YES-Associated Protein (YAP) in Murine Brain Endothelial Cells under Normal and Ischemic Conditions. 2015. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037357.

    MLA Style (8th edition)

  • Al-Waili, Daniah. "In Vitro Functional Study of YES-Associated Protein (YAP) in Murine Brain Endothelial Cells under Normal and Ischemic Conditions." Master's thesis, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037357

    Chicago Manual of Style (17th edition)

ucin1448037357
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This open access ETD is published by University of Cincinnati and OhioLINK.