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 stud...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-04-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32744-9 |
| _version_ | 1797845937475813376 |
|---|---|
| author | Seongmoon Jo Ahreum Baek Yoonhee Cho Sung Hoon Kim Dawoon Baek Jihye Hwang Sung-Rae Cho Hyun Jung Kim |
| author_facet | Seongmoon Jo Ahreum Baek Yoonhee Cho Sung Hoon Kim Dawoon Baek Jihye Hwang Sung-Rae Cho Hyun Jung Kim |
| author_sort | Seongmoon Jo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T17:48:05Z |
| format | Article |
| id | doaj.art-49b798b161ad41ad82ecca3fba482fda |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:48:05Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-49b798b161ad41ad82ecca3fba482fda2023-04-16T11:13:49ZengNature PortfolioScientific Reports2045-23222023-04-0113111010.1038/s41598-023-32744-9Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injurySeongmoon Jo0Ahreum Baek1Yoonhee Cho2Sung Hoon Kim3Dawoon Baek4Jihye Hwang5Sung-Rae Cho6Hyun Jung Kim7Department and Research Institute of Rehabilitation Medicine, Yonsei University College of MedicineDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of MedicineDepartment of Medicine, Yonsei University College of MedicineDepartment of Rehabilitation Medicine, Yonsei University Wonju College of MedicineDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of MedicineDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of MedicineDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of MedicineDepartment of Rehabilitation Medicine, Nowon Eulji Medical Center, Eulji University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-023-32744-9 |
| spellingShingle | Seongmoon Jo Ahreum Baek Yoonhee Cho Sung Hoon Kim Dawoon Baek Jihye Hwang Sung-Rae Cho Hyun Jung Kim Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury Scientific Reports |
| title | Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury |
| title_full | Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury |
| title_fullStr | Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury |
| title_full_unstemmed | Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury |
| title_short | Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury |
| title_sort | therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia reperfusion injury |
| url | https://doi.org/10.1038/s41598-023-32744-9 |
| work_keys_str_mv | AT seongmoonjo therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT ahreumbaek therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT yoonheecho therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT sunghoonkim therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT dawoonbaek therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT jihyehwang therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT sungraecho therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury AT hyunjungkim therapeuticeffectsofpolydeoxyribonucleotideinaninvitroneuronalmodelofischemiareperfusioninjury |