Androgen receptor contributes to microglial/macrophage activation in rats with intracranial hemorrhage by mediating the JMJD3/Botch/Notch1 axis
| Autor: | Xingzhong Hu, Dai Junxia, Sun Jun, Xiaoxiang Chen, Chen Maohua |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Jumonji Domain-Containing Histone Demethylases Rats Sprague-Dawley Downregulation and upregulation medicine Animals cardiovascular diseases Receptor Notch1 Transcription factor Intracerebral hemorrhage Microglia biology Microarray analysis techniques business.industry General Neuroscience Macrophages Macrophage Activation medicine.disease nervous system diseases Rats Androgen receptor medicine.anatomical_structure Apoptosis Receptors Androgen Cancer research biology.protein Demethylase business Intracranial Hemorrhages gamma-Glutamylcyclotransferase Signal Transduction |
| Zdroj: | Neuroscience letters. 765 |
| ISSN: | 1872-7972 |
| Popis: | Intracerebral hemorrhage (ICH) is a leading medical problem and has no effective treatment approach up until now. The transcription factor androgen receptor (AR) has been indicated in the cerebrovascular function recently. However, its participation in ICH remains unclear. The present study aims to expound the regulation of AR in microglia/macrophage phenotypes and the secondary brain injury in a rat model with ICH, and to discuss the involved pathway. Following the induction of ICH in rats, we found that ICH led to increased mNSS score, enhanced microglial activity, and promoted levels of inflammatory factors and apoptosis of brain cells. Using microarray analysis, AR was found to be significantly overexpressed in ICH rat brain tissues. AR repressed the transcription of Jumonji d3 (JMJD3, histone 3 demethylase). JMJD3 inhibited the methylation of Botch and promoted the activity of Notch1. JMJD3 hampered microglial activity and ameliorated secondary brain injury in rats, whereas upregulation of AR or downregulation of Botch reversed the protective effects of JMJD3. In conclusion, we found that AR promoted microglial activation and secondary brain injury via transcriptionally repressing JMJD3 and mediating the subsequent Botch/Notch1 pathway, which may provide novel insights into therapeutic options for the treatment of ICH. |
| Databáze: | OpenAIRE |
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