Data from: HIF prolyl hydroxylase 2/3 deletion disrupts astrocytic integrity and exacerbates neuroinflammation
Creators
- 1. Charité
- 2. Max Delbrück Center for Molecular Medicine
- 3. TU Dresden
Description
Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced Phd2/3 deletion in experimental autoimmune encephalomyelitis (EAE) in a therapeutic approach that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases.
Notes
Salmon output data can be further analyzed by R based package DESeq2.
Funding provided by: Deutsche Forschungsgemeinschaft
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001659
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