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STAT3 precedes HIF1? transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

ABSTRACT: Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation. Hypoxia has been widely known to stabilise the transcription factor hypoxia inducible factor 1-alpha (HIF1?) and mediate the induction of hypoxic transcriptional programs after ischemia. However, we find that the transcription factors Jun Proto-Oncogene (c-JUN), Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells (NF?B) and signal transducer and activator of transcription 3 (STAT3) bind genes regulated after 2hours (hs) of omitted glucose and oxygen before HIF1?. Potent HIF1? responses require 6hs of hypoxia to substantiate transcriptional regulation comparable to either c-JUN or STAT3. Phosphorylated STAT3 protein is at its highest after 5 min of oxygen and glucose (OGD) deprivation, whereas maximum HIF1? stabilisation requires 120 min. We show that STAT3 regulates angiogenic and metabolic pathways before HIF1?, suggesting that HIF1? is not the initiating trans-acting factor in the response of pericytes to ischemia.

SUBMITTER: Carlsson R

PROVIDER: S-EPMC5843348 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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STAT3 precedes HIF1α transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

Carlsson Robert R Özen Ilknur I Barbariga Marco M Gaceb Abderahim A Roth Michaela M Paul Gesine G

PloS one 20180308 3

Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pe ...[more]

PMID: 29518129

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Dataset Information

STAT3 precedes HIF1? transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

Publications

STAT3 precedes HIF1α transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

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