Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
SorCS2 facilitates release of endostatin from astrocytes and controls post-stroke angiogenesis. / Malik, Anna R; Lips, Janet; Gorniak-Walas, Malgorzata et al.
In: Glia, Vol. 68, No. 6, 06.2020, p. 1304-1316.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - SorCS2 facilitates release of endostatin from astrocytes and controls post-stroke angiogenesis
AU - Malik, Anna R
AU - Lips, Janet
AU - Gorniak-Walas, Malgorzata
AU - Broekaart, Diede W M
AU - Asaro, Antonino
AU - Kuffner, Melanie T C
AU - Hoffmann, Christian J
AU - Kikhia, Majed
AU - Dopatka, Monika
AU - Boehm-Sturm, Philipp
AU - Mueller, Susanne
AU - Dirnagl, Ulrich
AU - Aronica, Eleonora
AU - Harms, Christoph
AU - Willnow, Thomas E
N1 - © 2020 The Authors. Glia published by Wiley Periodicals, Inc.
PY - 2020/6
Y1 - 2020/6
N2 - SorCS2 is an intracellular sorting receptor of the VPS10P domain receptor gene family recently implicated in oxidative stress response. Here, we interrogated the relevance of stress-related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy brain, expression of SorCS2 was massively induced in astrocytes surrounding the ischemic core in mice following stroke. Post-stroke induction was likely a result of increased levels of transforming growth factor β1 in damaged brain tissue, inducing Sorcs2 gene transcription in astrocytes but not neurons. Induced astrocytic expression of SorCS2 was also seen in stroke patients, substantiating the clinical relevance of this observation. In astrocytes in vitro and in the mouse brain in vivo, SorCS2 specifically controlled release of endostatin, a factor linked to post-stroke angiogenesis. The ability of astrocytes to release endostatin acutely after stroke was lost in mice deficient for SorCS2, resulting in a blunted endostatin response which coincided with impaired vascularization of the ischemic brain. Our findings identified activated astrocytes as a source for endostatin in modulation of post-stroke angiogenesis, and the importance of the sorting receptor SorCS2 in this brain stress response.
AB - SorCS2 is an intracellular sorting receptor of the VPS10P domain receptor gene family recently implicated in oxidative stress response. Here, we interrogated the relevance of stress-related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy brain, expression of SorCS2 was massively induced in astrocytes surrounding the ischemic core in mice following stroke. Post-stroke induction was likely a result of increased levels of transforming growth factor β1 in damaged brain tissue, inducing Sorcs2 gene transcription in astrocytes but not neurons. Induced astrocytic expression of SorCS2 was also seen in stroke patients, substantiating the clinical relevance of this observation. In astrocytes in vitro and in the mouse brain in vivo, SorCS2 specifically controlled release of endostatin, a factor linked to post-stroke angiogenesis. The ability of astrocytes to release endostatin acutely after stroke was lost in mice deficient for SorCS2, resulting in a blunted endostatin response which coincided with impaired vascularization of the ischemic brain. Our findings identified activated astrocytes as a source for endostatin in modulation of post-stroke angiogenesis, and the importance of the sorting receptor SorCS2 in this brain stress response.
U2 - 10.1002/glia.23778
DO - 10.1002/glia.23778
M3 - Journal article
C2 - 31898841
VL - 68
SP - 1304
EP - 1316
JO - Glia
JF - Glia
SN - 0894-1491
IS - 6
ER -