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Study · Animal study (in vivo) · mouse · 2025

8 results

FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.

Hu Z, Li F, Hu C, Shan Q, Tang Z, Jiang M, Yi X, Chen X, Jin L, Wang X, Wang Y

Frontiers in bioengineering and biotechnology15 Jan 2026Cited by 1 (Europe PMC)

PMID41625068 (opens in a new tab)PMCIDPMC12852416 (opens in a new tab)DOI10.3389/fbioe.2025.1729166 (opens in a new tab)PepBankPUB-41625068
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Summary

ObjectivesEndothelial cell dysfunction during aging is a key driver of vascular aging and related diseases; however, effective strategies to selectively eliminate senescent endothelial cells and restore vascular function remain lacking. FOXO4-DRI, a novel peptide-based intervention, specifically disrupts the interaction between FOXO4 and P53, thereby inducing apoptosis in senescent cells. This study innovatively focuses on the mechanism by which FOXO4-DRI induces apoptosis in senescent endothelial cells, demonstrating that it functions by activating the p53/BCL-2/Caspase-3 signaling pathway to promote selective apoptosis of these cells. FOXO4-DRI significantly improves vascular function and delays vascular aging. These findings not only enrich the molecular understanding of senescent cell clearance but also provide a novel strategy for precise targeting of endothelial cell senescence in therapeutic applications.Materials and methodsThis study aims to analyze the vascular function and aging status of the aorta in naturally aged mice and progeroid model mice following FOXO4-DRI injection. Additionally, it investigates changes in endothelial cell function in senescent endothelial cells induced by oxygen-glucose deprivation (OGD), as well as the protein expression and interaction in the FOXO4-P53 signaling pathway. To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4-DRI, followed by immunofluorescence and Western blotting experiments.ResultsInjection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function. Additionally, we found that FOXO4-DRI alleviates endothelial cell senescence induced by OGD, thereby enhancing endothelial cell function. Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells. Ultimately, this mechanism achieves the goal of inhibiting vascular aging.ConclusionFOXO4-DRI promotes the nuclear export of phosphorylated P53 by inhibiting the binding of FOXO4 to P53 in endothelial cells, thereby facilitating the apoptosis of senescent endothelial cells and alleviating aging.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In naturally aged and induced aging mice, FOXO4‑DRI injection suppressed aortic aging.

    In plain wordsIn mice, FOXO4‑DRI injection reduced signs of aging in the aorta.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseAortic aging
    Study

    mousen: not reported in source

    Naturally aged and progeroid model mice
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Injection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function.
    1 context sentence
    Summary · context
    This study aims to analyze the vascular function and aging status of the aorta in naturally aged mice and progeroid model mice following FOXO4-DRI injection.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In naturally aged and induced aging mice, FOXO4‑DRI injection improved aortic function.

    In plain wordsIn mice, FOXO4‑DRI injection improved how well the aorta worked.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseAortic function
    Study

    mousen: not reported in source

    Naturally aged and progeroid model mice
    Outcome group
    Vascular function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Injection of FOXO4-DRI in both naturally aged and induced aging mice effectively suppressed aortic aging and improved aortic function.
    1 context sentence
    Summary · context
    This study aims to analyze the vascular function and aging status of the aorta in naturally aged mice and progeroid model mice following FOXO4-DRI injection.
  3. 03LabIn vitro (cells)Efficacy outcome

    In oxygen-glucose deprivation induced senescent endothelial cells, FOXO4‑DRI alleviated senescence.

    In plain wordsIn cells, FOXO4‑DRI reduced senescence in blood vessel lining cells.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseEndothelial cell senescence
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Aging markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Additionally, we found that FOXO4-DRI alleviates endothelial cell senescence induced by OGD, thereby enhancing endothelial cell function.
    1 context sentence
    Summary · context
    Additionally, it investigates changes in endothelial cell function in senescent endothelial cells induced by oxygen-glucose deprivation (OGD), as well as the protein expression and interaction in the FOXO4-P53 signaling pathway.
  4. 04LabIn vitro (cells)Efficacy outcome

    In oxygen-glucose deprivation induced senescent endothelial cells, FOXO4‑DRI enhanced endothelial cell function.

    In plain wordsIn cells, FOXO4‑DRI improved the function of blood vessel lining cells.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseEndothelial cell function
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Vascular function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Additionally, we found that FOXO4-DRI alleviates endothelial cell senescence induced by OGD, thereby enhancing endothelial cell function.
    1 context sentence
    Summary · context
    Additionally, it investigates changes in endothelial cell function in senescent endothelial cells induced by oxygen-glucose deprivation (OGD), as well as the protein expression and interaction in the FOXO4-P53 signaling pathway.
  5. 05LabIn vitro (cells)Mechanism

    In senescent endothelial cells, co-immunoprecipitation showed that FOXO4‑DRI prevented the binding of FOXO4 to P53.

    In plain wordsIn cells, FOXO4‑DRI stopped FOXO4 from binding to P53.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseFOXO4 and P53 binding
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells.
    1 context sentence
    Summary · context
    To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4-DRI, followed by immunofluorescence and Western blotting experiments.
  6. 06LabIn vitro (cells)Mechanism

    In senescent endothelial cells, FOXO4‑DRI facilitated nuclear exclusion of phosphorylated P53.

    In plain wordsIn cells, FOXO4‑DRI helped move phosphorylated P53 out of the nucleus.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseNuclear exclusion of phosphorylated P53
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells.
    1 context sentence
    Summary · context
    To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4-DRI, followed by immunofluorescence and Western blotting experiments.
  7. 07LabIn vitro (cells)Mechanism

    In senescent endothelial cells, FOXO4‑DRI triggered BAX and cleaved caspase-3.

    In plain wordsIn cells, FOXO4‑DRI raised the cell death signals BAX and cleaved caspase-3.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseBAX and cleaved caspase-3
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells.
    1 context sentence
    Summary · context
    To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4-DRI, followed by immunofluorescence and Western blotting experiments.
  8. 08LabIn vitro (cells)Mechanism

    In senescent endothelial cells, FOXO4‑DRI led to apoptosis of senescent cells.

    In plain wordsIn cells, FOXO4‑DRI caused aged blood vessel lining cells to die.

    Peptide
    FOXO4-DRI
    Outcome
    IncreaseApoptosis of senescent endothelial cells
    Study

    n: not reported in source

    OGD-induced senescent endothelial cells
    Outcome group
    Cell viability and death · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Through co-immunoprecipitation (CO-IP) experiments, we discovered that FOXO4-DRI prevents the binding of FOXO4 to P53, facilitating the phosphorylated P53 nuclear exclusion, which subsequently trigger BAX and cleaved caspase-3, leading to the apoptosis of senescent cells.
    1 context sentence
    Summary · context
    To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4-DRI, followed by immunofluorescence and Western blotting experiments.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

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