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Updated: Jul 16, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis
Xianxin Kang1, Yanhui Cao1, Guodong Sun1
1Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, Postal Street, Nangang District, Harbin, 150000, Heilongjiang Province, People's Republic of China.
Abstract:
Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis.
Insights
Circular RNA circPTP4A2 promotes ischemic stroke (IS) by inhibiting beneficial M2 microglia polarization. Downregulating circPTP4A2 may offer a novel therapeutic strategy for IS treatment.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia polarization significantly influences outcomes in ischemic stroke (IS).
- Understanding the molecular mechanisms regulating microglia polarization is crucial for developing effective IS therapies.
Purpose of the Study:
- To investigate the role of circular RNA circPTP4A2 in regulating microglia polarization in the context of IS.
- To elucidate the molecular pathway involving circPTP4A2, miR-20b-5p, YTHDF1, and TIMP2 in IS.
Main Methods:
- Ischemic stroke models were established using MCAO/R and OGD/R treatments.
- Cerebral infarct size, cell vitality, and microglia polarization markers (CD16, CD206) were assessed.
- Molecular interactions were analyzed using dual-luciferase reporter, RIP, and RNA pull-down assays.
Main Results:
- circPTP4A2 was found to be upregulated in IS patients and contributed to cerebral injury.
- Knockdown of circPTP4A2 alleviated IS-induced brain damage and promoted M2 microglia polarization.
- circPTP4A2 sponges miR-20b-5p, leading to increased YTHDF1 expression, which enhances TIMP2 mRNA stability and activates the NF-κB pathway.
Conclusions:
- circPTP4A2 downregulation promotes M2 microglia polarization via the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis, thereby inhibiting IS development.
- Targeting circPTP4A2 represents a potential therapeutic strategy for mitigating ischemic stroke progression.
