title: The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.
abstract: In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8.
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, China. Electronic address: xcliu@mail.cmu.edu.cn.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, China.
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 Nanjing Street, Heping District, Shenyang 110001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; C498142:Eps8 protein, rat; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Ang1; Blood–spinal cord barrier; Eps8; SCMEC