Secretomics reveals gelatinase substrates at the blood-brain barrier that are 
implicated in astroglial barrier function

Burmeister, Miriam; Frauenstein, Annika; Kahms, Martin; Arends, Laura; Gerwien, Hanna; Deshpande, Tushar; Kuhlmann, Tanja; Gross, Catharina C. C.; Naik, Venu N. N.; Wiendl, Heinz; Klingauf, Juergen; Meissner, Felix; Sorokin, Lydia

doi:10.1126/sciadv.adg0686

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Secretomics reveals gelatinase substrates at the blood-brain barrier that are implicated in astroglial barrier function

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Frauenstein, Annika
Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society;

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Meissner, Felix
Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society;

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引用

Burmeister, M., Frauenstein, A., Kahms, M., Arends, L., Gerwien, H., Deshpande, T., Kuhlmann, T., Gross, C. C. C., Naik, V. N. N., Wiendl, H., Klingauf, J., Meissner, F., & Sorokin, L. (2023). Secretomics reveals gelatinase substrates at the blood-brain barrier that are implicated in astroglial barrier function. Science Advances, 9(29):. doi:10.1126/sciadv.adg0686.

引用: https://hdl.handle.net/21.11116/0000-000D-A35F-1

要旨

The gelatinases, matrix metalloproteinase 2 (MMP-2) and MMP-9, are key for leukocyte penetration of the brain parenchymal border in neuroinflammation and the functional integrity of this barrier; however, it is unclear which MMP substrates are involved. Using a tailored, sensitive, label-free mass spectrometry-based secretome approach, not previously applied to nonimmune cells, we identified 119 MMP-9 and 21 MMP-2 potential substrates at the cell surface of primary astrocytes, including known substrates (beta-dystroglycan) and a broad spectrum of previously unknown MMP-dependent events involved in cell-cell and cell-matrix interactions. Using neuroinflammation as a model of assessing compromised astroglial barrier function, a selection of the potential MMP substrates were confirmed in vivo and verified in human samples, including vascular cell adhesion molecule-1 and neuronal cell adhesion molecule. We provide a unique resource of potential MMP-2/MMP-9 substrates specific for the astroglia barrier. Our data support a role for the gelatinases in the formation and maintenance of this barrier but also in astrocyte-neuron interactions.