Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury.

Abstract

Polydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.

• Authors: Seongmoon Jo, Ahreum Baek, Yoonhee Cho, Sung Hoon Kim, Dawoon Baek, Jihye Hwang, Sung-Rae Cho, Hyun Jung Kim
• Journal: Scientific reports (Sci Rep) Vol. 13 Issue 1 Pg. 6004 (04 12 2023) ISSN: 2045-2322 [Electronic] England
• PMID: 37045900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Polydeoxyribonucleotides
• Janus Kinases
• STAT Transcription Factors

Topics

• Humans
• Polydeoxyribonucleotides (therapeutic use)
• Janus Kinases (metabolism)
• Signal Transduction
• STAT Transcription Factors (metabolism)
• Reperfusion Injury (metabolism)
• Ischemia (etiology)