Dataset Information

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

ABSTRACT: The[Q3] 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 spectrometryÃ¢â‚¬â€œbased 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 (ÃŽÂ²-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 moleculeÃ¢â‚¬â€œ1 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Mario Oroshi

LAB HEAD: Felix Meissner

PROVIDER: PXD043521 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	20200610_QX3_AnFr_ST00_Astrocytes_01_200615022254.raw	Raw
	20200610_QX3_AnFr_ST00_Astrocytes_02_200615043933.raw	Raw
	20200610_QX3_AnFr_ST00_Astrocytes_03.raw	Raw
	20200610_QX3_AnFr_ST00_Astrocytes_04.raw	Raw
	20200610_QX3_AnFr_ST00_Astrocytes_06.raw	Raw

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

Burmeister Miriam M Fraunenstein Annika A Kahms Martin M Arends Laura L Gerwien Hanna H Deshpande Tushar T Kuhlmann Tanja T Gross Catharina C CC Naik Venu N VN Wiendl Heinz H Klingauf Juergen J Meissner Felix F Sorokin Lydia L

Science advances 20230719 29

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 su ...[more]

PMID: 37467333

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