Sirt1 regulates microglial activation and inflammation following oxygen-glucose deprivation/reoxygenation injury by targeting the Shh/Gli-1 signaling pathway.

Abstract

BACKGROUND:

Cerebral ischemic injury leads to over-activation of microglia, which release pro-inflammatory factors that deteriorate neurological function during the acute phase of stroke. Thus, inhibiting microglial over-activation is crucial for reducing ischemic injury. Sirtuin 1 (Sirt1) has been shown to play a critical role in stroke, neurodegenerative diseases and aging. However, the effect of Sirt1 on the regulation of microglial activation following cerebral ischemic injury, as well as the underlying mechanism, remain unknown. Therefore, the purpose of the present study is to mainly investigate the effect of Sirt1 on oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N9 microglia following treatment with the Sirt1 agonists resveratrol and SRT1720 and the Sirt1 antagonist sirtinol.

METHODS:

Cell viability, Apoptosis, activation and inflammatory responses of microglia, expressions and activity of Shh signaling pathway proteins were detected by Cell Counting Kit 8, Flow Cytometry, immunocytochemistry, ELISA, and Western blotting, respectively.

RESULTS:

The results demonstrated that treatment with resveratrol or SRT1720 could inhibit the activation of microglia and inflammation during OGD/R. Moreover, these treatments also led to the translocation of the GLI family zinc finger-1 (Gli-1) protein from the cytoplasm to the nucleus and upregulated the expression of Sonic hedgehog (Shh), Patched homolog-1 (Ptc-1), smoothened frizzled class receptor and Gli-1. By contrast, the inhibition of Sirt1 using sirtinol had the opposite effect.

CONCLUSION:

These findings suggested that Sirt1 may regulate microglial activation and inflammation by targeting the Shh/Gli-1 signaling pathway following OGD/R injury. Schematic representation of Sirt1 regulating the microglial activation and inflammation following oxygen-glucose deprivation/reoxygenation injury via mediation of Shh/Gli-1 signaling pathway.

• Authors: Hongyan Liao, Jiagui Huang, Jie Liu, Huimin Zhu, Yue Chen, Xuemei Li, Jun Wen, Qin Yang
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 50 Issue 4 Pg. 3317-3327 (Apr 2023) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 36725745 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Glucose
• Hedgehog Proteins
• Oxygen
• Resveratrol
• SHH protein, human
• SIRT1 protein, human
• sirtinol
• Sirtuin 1
• Zinc Finger Protein GLI1

Topics

• Humans
• Glucose (metabolism)
• Hedgehog Proteins (metabolism)
• Inflammation (drug therapy, metabolism)
• Microglia (metabolism)
• Oxygen (metabolism)
• Resveratrol (pharmacology, metabolism)
• Signal Transduction
• Sirtuin 1 (metabolism)
• Stroke (metabolism)
• Zinc Finger Protein GLI1 (metabolism)