Vitronectin (VTN) is a glycoprotein in the blood and affects hemostasis. VTN is also present in the extracellular matrix of various organs but little is known about its function in healthy adult tissues. We show, in adult mice, that VTN is uniquely expressed by approximately half of the pericytes of subventricular zone (SVZ) where neurogenesis continues throughout life. Intracerebral VTN antibody injection or VTN knockout reduced neurogenesis as well as expression of pro-neurogenic CNTF, and anti-neurogenic LIF and IL-6. Conversely, injections of VTN, or plasma from VTN+/+, but not VTN-/- mice, increased these cytokines. VTN promoted SVZ neurogenesis when LIF and IL-6 were suppressed by co-administration of a gp130 inhibitor. Unexpectedly, VTN inhibited FAK signaling and VTN-/- mice had increased FAK signaling in the SVZ. Further, an FAK inhibitor or VTN increased CNTF expression, but not in conditional astrocytic FAK knockout mice, suggesting that VTN increases CNTF through FAK inhibition in astrocytes. These results identify a novel role of pericyte-derived VTN in the brain, where it regulates SVZ neurogenesis through co-expression of CNTF, LIF and IL-6. VTN-integrin-FAK and gp130 signaling may provide novel targets to induce neurogenesis for cell replacement therapies.
Pubmed ID: 30408465 RIS Download
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View all literature mentionsThis monoclonal targets alpha-Tubulin
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Ptk2b
View all literature mentionsThis polyclonal targets Phospho-Pyk2 (Tyr402)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis monoclonal targets ILK
View all literature mentionsThis polyclonal targets phospho-ILK (Ser246)
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View all literature mentionsThis monoclonal targets Mouse Vitronectin
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View all literature mentionsThis polyclonal targets Vitronectin antibody
View all literature mentionsThis polyclonal targets Aminopeptidase N/CD13
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View all literature mentionsThis polyclonal targets Mouse Vitronectin
View all literature mentionsThis monoclonal targets Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis polyclonal targets Doublecortin
View all literature mentionsThis polyclonal targets Vitronectin antibody
View all literature mentionsMus musculus with name B6;129X1-Ptk2tm1Lfr/Mmucd from MMRRC.
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