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The murine embryonic blood-brain barrier (BBB) consists of endothelial cells (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for inducing vascular stability, signaling pathways in PCs that regulate EC morphogenesis during BBB development remain unexplored. Herein, we find that murine embryos lacking the transforming growth factor β (TGF-β) receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH). The germinal matrix (GM) is a highly vascularized structure rich in neuronal and glial precursors. We show that GM microvessels of mutants display abnormal dilation, reduced PC coverage, EC hyperproliferation, reduced basement membrane collagen, and enhanced perivascular matrix metalloproteinase activity. Furthermore, ALK5-depleted PCs downregulate tissue inhibitor of matrix metalloproteinase 3 (TIMP3), and TIMP3 administration to mutants improves endothelial morphogenesis and attenuates GMH-IVH. Overall, our findings reveal a key role for PC ALK5 in regulating brain endothelial morphogenesis and a substantial therapeutic potential for TIMP3 during GMH-IVH.
Pubmed ID: 29456135 RIS Download
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This polyclonal secondary targets Immunoglobulins
View all literature mentionsThis monoclonal targets TIMP-3 (Tissue Inhibitor of Metalloproteinases-3), aa 170-188
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Smad2/3
View all literature mentionsThis monoclonal targets Phospho-Smad2 (Ser465/467) (138D4) Rabbit mAb
View all literature mentionsThis polyclonal targets TGF beta Receptor I
View all literature mentionsThis monoclonal targets CD16/CD32
View all literature mentionsThis unknown targets Digoxigenin
View all literature mentionsThis polyclonal targets Chicken IgY
View all literature mentionsThis unknown targets Rabbit IgG, Light Chain Specific
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse PDGF R beta
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Col4a3
View all literature mentionsThis polyclonal targets Collagen I
View all literature mentionsThis polyclonal targets MMP2
View all literature mentionsThis polyclonal targets MMP9 - Whole molecule
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis recombinant monoclonal targets Smad3 (phospho S423 + S425)
View all literature mentionsThis monoclonal targets Chemical BrdU
View all literature mentionsThis unknown targets Ki-67
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis monoclonal targets CD144 (VE-Cadherin)
View all literature mentionsMus musculus with name STOCK Tgfbr1tm1.1Karl/KulJ from IMSR.
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Tg(Pdgfrb-cre)9Rha from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
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