Per2 deficiency in microglia alleviates motor dysfunction by inhibiting ferroptosis in spinal cord injury [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA1294841 | ENA |
REPOSITORIES: ENA
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Project description:Microglia play significant roles in spinal cord injury (SCI) progression. Previous studies have suggested that ferroptosis plays a crucial role in exacerbating neuronal death following SCI; however, the role of microglial ferroptosis in SCI and the underlying mechanisms remain elusive. Here, we elucidate that lipid droplets accumulate in microglia to facilitate microglial ferroptosis after SCI. Notably, microglial ferroptosis peaks at 3 days post-injury, after which it decreases. Microglial Period 2 (Per2) expression is elevated after SCI in vivo; this change is highly synchronized with the changes in microglial ferroptosis. Microglia-specific Per2 knockout promoted neurological function recovery by suppressing microglial ferroptosis. In vitro, Per2 overexpression and deficiency amplified and mitigated microglial ferroptosis, respectively. RNA-seq indicated that Gpx4 was downregulated by Per2. Coimmunoprecipitation demonstrated that Per2 directly interacted with PPARα. Overall, our results indicate that Per2 determines the susceptibility of microglial ferroptosis via the PPARα-Gpx4 axis after SCI.
2025-08-20 | GSE303249 | GEO
Project description:Microglia play significant roles in spinal cord injury (SCI) progression. Previous studies have suggested that ferroptosis plays a crucial role in exacerbating neuronal death following SCI; however, the role of microglial ferroptosis in SCI and the underlying mechanisms remain elusive. Here, we elucidate that lipid droplets accumulate in microglia to facilitate microglial ferroptosis after SCI. Notably, microglial ferroptosis peaks at 3 days post-injury, after which it decreases. Microglial Period 2 (Per2) expression is elevated after SCI in vivo; this change is highly synchronized with the changes in microglial ferroptosis. Microglia-specific Per2 knockout promoted neurological function recovery by suppressing microglial ferroptosis. In vitro, Per2 overexpression and deficiency amplified and mitigated microglial ferroptosis, respectively. RNA-seq indicated that Gpx4 was downregulated by Per2. Coimmunoprecipitation demonstrated that Per2 directly interacted with PPARα. Overall, our results indicate that Per2 determines the susceptibility of microglial ferroptosis via the PPARα-Gpx4 axis after SCI.
2025-08-20 | GSE303325 | GEO
Project description:Per2 deficiency in microglia alleviates motor dysfunction by inhibiting ferroptosis in spinal cord injury
| PRJNA1294408 | ENA
Project description: Not available
| S-EPMC12357938 | biostudies-literature
Project description:Microglia are more susceptible to ferroptosis compared to neurons and astrocytes, which may compromise their phagocytic and clearance capabilities of α-synuclein (α-syn) in Parkinson’s disease (PD). While the beneficial effects of physical exercise (PE) on reducing α-syn deposition in PD have been highlighted, the role of PE in modulating microglial ferroptosis remains unclear. This study focuses on the impact of exercise on inhibiting microglial ferroptosis and mitigating α-syn accumulation. We demonstrate that voluntary exercise effectively inhibits microglial ferroptosis. Mechanistically, PE-induced upregulation of SLC7A11 inhibits microglial ferroptosis by suppressing ALOX12, thereby enhancing microglial phagocytosis and clearance of α-syn, which is paralleled by improvements in neurological function in PD mice. Collectively, these findings not only underscore the critical role of microglial ferroptosis in the pathological progression of PD but also elucidate the molecular mechanism by which PE attenuates microglial ferroptosis via the SLC7A11/ALOX12 axis.
2025-09-29 | GSE309457 | GEO
Project description:Purpose: 5-FU resistance is considered to be a possible reason for the failure of conventional drug treatment of colorectal cancer (CRC). Recently, salinomycin (SAL), as a selective inhibitor of cancer stem cells (CSCs), has been used to sensitize and attenuate a variety of solid tumor chemotherapy drugs. In our study, our goal was to combine SAL with 5-FU to explore whether increase the sensitivity of CRC to 5-FU and the molecular mechanism that involved in enhancing 5-FU sensitivity and promoting tumor cell chemotherapeutic death. Methods: ComboSyn software was used to study whether dual drug combinations synergistically promote each other and their dosage. CCK8, EdU and Annexin V/PI assays were used to study the cell proliferation and apoptosis of SW480 and HCT116 cells in response to SAL single-drug and dual-drug co-treatment. Cell cycle staining was used to assess cycle arrest. Wound healing and migration and invasion experiments were used to identify changes in migration and invasion capabilities under the influence of different drugs. Transcriptome sequencing is used to explore the molecular mechanisms of drugs. ROS fluorescence staining and MDA level measurement were used to confirm the changes in ferroptosis levels of SW480 and HCT116 cells after drug treatment. Nude xenograft mice were used to detect antitumor in vivo. Changes in the protein level expression of ferroptosis GPX4 and SLC7A11 were also determined in the treated cells.Results: SAL alone and combination of 5-FU were found to significantly increase cell mortality and apoptosis. At the same time, our results show that the blending of SAL and 5-FU not only inhibits the proliferation, migration, and invasion of CRC colorectal cancer cell lines in vivo and in vitro, but also promotes ferroptosis of CRC cell lines by downregulating the expression of GPX4 and SLC7A11. It may provide more and novel solutions and treatment perspectives for 5-FU or other drug-resistant chemotherapy strategies for CRC patients.Conclusions: SAL inhibiting colorectal cancer whose effect is achieved by reducing GPX4 and SLC7A11 protein levels to mediate ferroptosis activation in collaboration with 5-fluorouracil.
2025-06-21 | E-MTAB-15206 | biostudies-arrayexpress
Project description:Mitochondria play a critical role in initiating and amplifying ferroptosis. VDAC1 embedded in the mitochondrial outer membrane, exerts a crucial role in regulation of ferroptosis. However, the mechanisms of VDAC1 oligomerization in regulating ferroptosis are not well elucidated. Here, we identified that VSTM2L, a novel VDAC1 binding protein, is positively associated with prostate cancer (PCa) progression, and a key regulator of ferroptosis. Moreover, VSTM2L knockdown in PCa cells enhanced the sensibility of RSL3-induced ferroptosis. Mechanistically, VSTM2L forms complex with VDAC1 and HK2, enhancing their binding affinity and preventing VDAC1 oligomerization, thereby inhibiting ferroptosis and maintaining mitochondria homeostasis in vitro and in vivo. Collectively, our findings reveal a pivotal role for VSTM2L in driving ferroptosis resistance and highlight its potential as a ferroptosis-inducing therapeutic target for the treatment of PCa.
2025-05-07 | PXD052173 | Pride
Project description:Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as a mode of action for CD8+T cell (CTL)-mediated keloid killing. Mechanistically, keloid IFNγ deficiency in combination with reduced DNMT3A increase the expression of SPOCD1, thereby promoting KFs’ proliferation and inhibiting its ferroptosis. Moreover, keloid SPOCD1 deficiency attenuates KFs progression and extracellular matrix (ECM) deposition. Reducing IFNγ and SPOCD1 simultaneously can increase the positive rate of reactive oxygen species (ROS) and promote mitochondrial shrinkage. Ex-vivo explant keloid culture has also confirmed that the reduction of SPOCD1 helps to reduce the proliferation rate of KFs, inhibit the angiogenesis of keloid scars, and thus inhibit keloid formation. Thus, IFNγ signaling paired with SPOCD1 is a natural keloid ferroptosis promoting mechanism and a mode of action of CTLs. Targeting SPOCD1 pathway is a potential anti-keloid approach.
2025-01-22 | GSE280420 | GEO
Project description:MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis
| PRJNA1062043 | ENA
Project description:Thymosin α1 Inhibiting Ferroptosis of Dental Pulp Cells in Pulpitis
| PRJNA1179354 | ENA