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Roles of Prokineticin 2 in Subarachnoid Hemorrhage-Induced Early Brain Injury via Regulation of Phenotype Polarization in Astrocytes.

Abstract：

:Previous studies have postulated that neuroinflammation can induce two different types of reactive astrocytes, A1 and A2. A1 astrocytes may be harmful, whereas A2 astrocytes may be protective. Specifically, prokineticin 2 (PK2) has been shown to regulate neuron-astrocyte signaling mechanism by promoting an alternative A2-protective phenotype in astrocytes. This study aimed to examine the role of PK2 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH). SAH-induced astrocytic activation was confirmed by Western blotting. We confirmed C3 and PTX3 as appropriate reactivity markers for discriminating A1 and A2 astrocytes, respectively. We also observed SAH-induced astrocytic activation in SAH patients. The increase of PK2 in neurons after SAH in both humans and rats suggested a possible relationship between PK2 and SAH pathology. PK2 knockdown promoted an A1 astrocytic phenotype with upregulation of neurodegenerative indicators, while intravascular injection of recombinant PK2 (rPK2) promoted A2 astrocytic phenotype and reduced SAH-induced neuronal injury and behavioral dysfunction. Finally, we identified that tumor necrosis factor alpha (TNF-α) was sufficient to elevate the protein level of PK2 in neurons and enhance astrocytic activation in vitro. Moreover, rPK2 selectively promoted astrocytic polarization to an A2 phenotype under a TNF-α stimulus and induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), suggesting that SAH-induced increases in PK2 may function as an endogenous mechanism for self-repair. Collectively, our findings support that enhancing PK2 expression or administration of rPK2 may induce a selective modulation of astrocytic polarization to a protective phenotype following SAH-like stimuli.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Ma M,Li H,Wu J,Zhang Y,Shen H,Li X,Wang Z,Chen G

doi

10.1007/s12035-020-01990-7

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

3744-3758

issue

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-020-01990-7

journal_volume

pub_type

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Roles of Prokineticin 2 in Subarachnoid Hemorrhage-Induced Early Brain Injury via Regulation of Phenotype Polarization in Astrocytes.