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Is foxo4 upregulated in senescent cells?

Transcription factor

Pulmonary fibrosis

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Yes, FOXO4 is indeed upregulated in senescent cells. Studies have shown that FOXO4 is progressively upregulated after senescence induction and is found in damage foci in senescent cells, where it inhibits apoptosis through interacting with p53 . Additionally, FOXO4 has been found to be specifically expressed in human Leydig cells and translocates to the nucleus in the elderly, contributing to decreased testosterone synthesis. By disrupting the FOXO4-p53 interaction, a specific FOXO4 blocker, FOXO4-DRI, selectively induces p53 nuclear exclusion and apoptosis in senescent Leydig cells, highlighting the role of FOXO4 in maintaining the viability of senescent cells . These findings collectively support the upregulation and functional significance of FOXO4 in senescent cells.

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Open access•Journal Article•DOI Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes Yuzhao Huang, Yuchen He, Meagan J. Makarcyzk, Hang Lin - Show less +3 more 29 Apr 2021-Frontiers in Bioengineering and Biotechnology 8 Citations	FOXO4-DRI selectively removes senescent cells but does not upregulate FOXO4. It targets senescent chondrocytes by disrupting FOXO4-p53 interaction, inducing apoptosis, and enhancing cartilage quality.
Open access•Journal Article•DOI FOXO4 peptide targets myofibroblast ameliorates bleomycin‐induced pulmonary fibrosis in mice through ECM‐receptor interaction pathway Xiaodan Han, T.Y Yuan, Junliang Zhang, Yonggang Shi, Deguan Li, Yinping Dong, Saijun Fan - Show less +6 more 05 May 2022-Journal of Cellular and Molecular Medicine 8 Citations	Yes, FOXO4-DRI targets myofibroblasts in pulmonary fibrosis by decreasing senescent cells and downregulating the senescence-associated secretory phenotype, indicating FOXO4 involvement in senescent cell regulation.
Open access DNA Damage Induced Cell Fates during Aging Marjolein Baar 12 Jun 2019 3 Citations	Yes, FOXO4 is progressively upregulated in senescent cells, where it inhibits apoptosis by interacting with p53, as highlighted in the research paper.
Journal Article•DOI FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA Raju Mandal, Klara Kohoutova, Olivia Petrvalska, Matej Horvath, Pavel Srb, Vaclav Veverka, Veronika Obsilova, Tomas Obsil - Show less +7 more 09 Apr 2022-Protein Science 2 Citations	FOXO4 interacts with p53 to induce cellular senescence by upregulating p21, but the paper does not specify if FOXO4 itself is upregulated in senescent cells.

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What are the biomarkers of cell senescent in cancer?5 answersCell senescence in cancer can be identified by specific biomarkers such as senescence-associated β-galactosidase (SA-β-gal), cell division cycle 7-related protein kinase, partitioning defective three homolog B, putative ATP-dependent RNA helicase DHX57. These biomarkers play a crucial role in detecting therapy-induced senescence (TIS) in cancer cells, aiding in prognosis and treatment strategies. Studies have shown that the expression of markers like p21CIP1, H3K9Me3, and Lamin B1 can indicate a senescence-like phenotype in breast cancer samples post neoadjuvant chemotherapy, with Lamin B1 showing promise as a predictive marker for senescence detection. The identification of these biomarkers is essential for understanding the impact of senescence on cancer progression and developing targeted therapies for age-related diseases like cancer.

Can senescent cells show cell proliferation?5 answersSenescent cells can show cell proliferation, as indicated by the presence of the proliferation marker Ki-67 in the tumor invasion front of prostate cancer cells. Additionally, senescent cells have been shown to stimulate skin carcinogenesis by elevating p38MAPK and MAPK/ERK signaling. However, the replicative capacity of senescent endothelial cells (ECs) can be improved by cultivation on micro-structured surfaces with anisotropic topography, leading to enhanced cell proliferation. The senescence-associated secretory phenotype (SASP) secreted by senescent cells can have pro-inflammatory and growth-stimulatory effects, contributing to different stages of carcinogenesis. In a study using HeLa cells, the morphology of senescent cells varied depending on the culture platform, with flattened morphology observed in 2D culture systems but reduced artifact in 3D scaffolds, suggesting that the 3D scaffolds suppress senescence in cells.

Can mRNA therapy be used to clear senescent cells?5 answersmRNA therapy has the potential to be used to clear senescent cells, which are implicated in age-related declines and diseases. Senescent cells accumulate in tissues with advancing age and can have detrimental effects. Understanding the molecular mechanisms by which MicroRNAs influence senescence can enable diagnostic and therapeutic opportunities directed at senescent cells. Additionally, recent progress has been made in the field of senescent cell clearance and various anti-aging strategies, including the targeted killing of senescent cells. Removing senescent cells from the body has been shown to delay the occurrence of aging-associated diseases. While the abstracts do not explicitly mention mRNA therapy for clearing senescent cells, the potential of mRNA therapeutics in clinical applications is highlighted, indicating that mRNA therapy could be explored as a potential approach for clearing senescent cells.

What is role of transcriptional factor FOXO1 in progression of gestational diabetes?4 answersThe transcription factor FOXO1 plays a role in the progression of gestational diabetes. It is involved in regulating cellular processes such as apoptosis, autophagy, oxidative stress, and metabolic dysregulation. FOXO1's function depends on the modulation of downstream targets, including apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators. In pregnant women with gestational diabetes mellitus (GDM), FOXO1 expression is higher in the placenta and omental adipose tissue compared to those with normal glucose tolerance. FOXO1 has been found to have a potential role as a pro-inflammatory factor in GDM and may be involved in the development of insulin resistance through interaction with tumor necrosis factor-α (TNF-α). These findings suggest that FOXO1 may contribute to the pathogenesis of gestational diabetes by affecting various cellular processes and interacting with inflammatory factors.

What is role of transcriptional factor FOXO1 in progression of gdm?5 answersThe transcription factor FOXO1 plays a role in the progression of gestational diabetes mellitus (GDM). FOXO1 is involved in various diseases, including cardiovascular diseases, diabetes, and cancer. In the context of GDM, FOXO1 is implicated in cardiac hypertrophy, which can lead to heart failure and cardiovascular events. FOXO1 regulates cardiac growth/protein synthesis, calcium homeostasis, cell apoptosis, and autophagy, and is controlled by upstream signaling molecules such as phosphatidylinositol 3-kinase/Akt and AMP-activated protein kinase. It also regulates downstream transcription proteins like ubiquitin ligases muscle RING finger 1/muscle atrophy F-box and calcineurin/nuclear factor of activated T cells. Targeted regulation of FOXO1 is considered an effective method of intervening in myocardial hypertrophy, suggesting its potential role in the treatment of cardiac hypertrophy associated with GDM.

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