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FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.
Kong YX, Li ZS, Liu YB, Pan B, Fu X, Xiao R, Yan L. Kong YX, et al. Commun Biol. 2025 Feb 24;8(1):299. doi: 10.1038/s42003-025-07738-0. Commun Biol. 2025. PMID: 39994346 Free PMC article.
We further demonstrate that a senolytic FOXO4-D-retro-inverso-isoform peptide (FOXO4-DRI) promotes apoptosis and decreases G0/G1 phase cells in pro-senescence models of keloid organ cultures and fibroblasts, accompanied with p53-pS15 nuclear exclusion. Our study ind …
We further demonstrate that a senolytic FOXO4-D-retro-inverso-isoform peptide (FOXO4-DRI) promotes apoptosis and decreases G0/ …
FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells.
Li Y, Zhang C, Cheng H, Lv L, Zhu X, Ma M, Xu Z, He J, Xie Y, Yang X, Liang X, Deng C, Liu G. Li Y, et al. Exp Gerontol. 2024 Oct 1;195:112522. doi: 10.1016/j.exger.2024.112522. Epub 2024 Jul 19. Exp Gerontol. 2024. PMID: 39025385 Free article.
Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of c …
Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed …
The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.
Bourgeois B, Spreitzer E, Platero-Rochart D, Paar M, Zhou Q, Usluer S, de Keizer PLJ, Burgering BMT, Sánchez-Murcia PA, Madl T. Bourgeois B, et al. Nat Commun. 2025 Jul 1;16(1):5672. doi: 10.1038/s41467-025-60844-9. Nat Commun. 2025. PMID: 40593617 Free PMC article.
We recently identified the FOXO4 - p53 axis as pivotal in maintaining the viability of senescent cells, and that senescent cells can be targeted selectively with the senolytic peptide FOXO4-DRI. Here, we solve the solution NMR structural models of the p53 transactiv …
We recently identified the FOXO4 - p53 axis as pivotal in maintaining the viability of senescent cells, and that senescent cells can be targ …
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.
Zhang C, Xie Y, Chen H, Lv L, Yao J, Zhang M, Xia K, Feng X, Li Y, Liang X, Sun X, Deng C, Liu G. Zhang C, et al. Aging (Albany NY). 2020 Jan 20;12(2):1272-1284. doi: 10.18632/aging.102682. Epub 2020 Jan 20. Aging (Albany NY). 2020. PMID: 31959736 Free PMC article.
In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. These findings reveal the therapeutic potential of FOXO4-DRI for the treatment of male late-onset hypogonadism.. …
In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion i …
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.
Born E, Lipskaia L, Breau M, Houssaini A, Beaulieu D, Marcos E, Pierre R, Do Cruzeiro M, Lefevre M, Derumeaux G, Bulavin DV, Delcroix M, Quarck R, Reen V, Gil J, Bernard D, Flaman JM, Adnot S, Abid S. Born E, et al. Circulation. 2023 Feb 21;147(8):650-666. doi: 10.1161/CIRCULATIONAHA.122.058794. Epub 2022 Dec 14. Circulation. 2023. PMID: 36515093
SC clearance was obtained by a suicide gene (p16 promoter-driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell-permeable FOXO4-p53 interfering peptide [FOXO4-DRI]), and p16 inactivation in p16(LUC/LUC) mice. We investigated pulmonary hyp …
SC clearance was obtained by a suicide gene (p16 promoter-driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell- …
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. Hu Z, et al. Front Bioeng Biotechnol. 2026 Jan 15;13:1729166. doi: 10.3389/fbioe.2025.1729166. eCollection 2025. Front Bioeng Biotechnol. 2026. PMID: 41625068 Free PMC article.
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. ...Additionally, we found that FOXO4-DRI allev …
To assess the impact of FOXO4-DRI on endothelial cell senescence, the senescent endothelial cells were treated with FOXO4 …
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.
Huang Y, He Y, Makarcyzk MJ, Lin H. Huang Y, et al. Front Bioeng Biotechnol. 2021 Apr 29;9:677576. doi: 10.3389/fbioe.2021.677576. eCollection 2021. Front Bioeng Biotechnol. 2021. PMID: 33996787 Free PMC article.
Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in t …
Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively …
Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.
Meng J, Li Y, Wan C, Sun Y, Dai X, Huang J, Hu Y, Gao Y, Wu B, Zhang Z, Jiang K, Xu S, Lovell JF, Hu Y, Wu G, Jin H, Yang K. Meng J, et al. JCI Insight. 2021 Dec 8;6(23):e146334. doi: 10.1172/jci.insight.146334. JCI Insight. 2021. PMID: 34877934 Free PMC article.
Specific induction of senescence-like CAF apoptosis using FOXO4-DRI, a FOXO4-p53-interfering peptide, resulted in remarkable effects on radiosensitizing NSCLC cells in vitro and in vivo. In addition, in this study, we also uncovered an obvious therapeutic effect of …
Specific induction of senescence-like CAF apoptosis using FOXO4-DRI, a FOXO4-p53-interfering peptide, resulted in remarkable e …
FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.
Liu Y, Hou Q, Wang R, Liu Y, Cheng Z. Liu Y, et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2393-2403. doi: 10.1007/s00210-023-02452-2. Epub 2023 Apr 19. Naunyn Schmiedebergs Arch Pharmacol. 2023. PMID: 37074394
In this research, we explored the effect of FOXO4-DRI on bleomycin (BLM)-induced PF mouse model and activated fibroblasts model. The animal group of FOXO4-DRI therapeutic administration shows a milder pathologic change and less collagen deposition comp …
In this research, we explored the effect of FOXO4-DRI on bleomycin (BLM)-induced PF mouse model and activated fibroblasts mode …
FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.
Han X, Yuan T, Zhang J, Shi Y, Li D, Dong Y, Fan S. Han X, et al. J Cell Mol Med. 2022 Jun;26(11):3269-3280. doi: 10.1111/jcmm.17333. Epub 2022 May 5. J Cell Mol Med. 2022. PMID: 35510614 Free PMC article.
However, it remains unknown if FOXO4-DRI could clear senescent cells in PF and reverse this disease. In this study, we explored the effect of FOXO4-DRI on bleomycin (BLM)-induced PF mouse model. ...Above all, FOXO4-DRI ameliorates BLM-ind …
However, it remains unknown if FOXO4-DRI could clear senescent cells in PF and reverse this disease. In this study, we explore …
17 results