A Review of FoxO1-Regulated Metabolic Diseases and Related Drug Discoveries

Peng, Shiming; Li, Wei; Hou, Nannan; Huang, Niu

doi:10.3390/cells9010184

Cited by 88 publications

(70 citation statements)

References 61 publications

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“…Once activated, AKT phosphorylates many downstream targets, including FoxO1 ( 47 ). FoxO1 transcriptionally mediates pathways responsible for many metabolic diseases that are translated by the FoxO1 gene, a member of FoxO genes belonging to the transcription factor (TF) family ( 48 ). The PI3K/AKT pathway has been reported to be important for Treg development both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Chen

et al. 2020

Front. Immunol.

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Autoimmune uveitis (AU), being one of the sight-threatening ocular inflammatory disorders, has been widely regarded by ophthalmologists and immunologists as a great challenge. Apremilast, a phosphodiesterase-4 inhibitor (PDE4i), which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of active psoriatic arthritis in 2014, has been attracting researchers, who are exploring its efficiency and mechanism on uveitis. In this study, we used an experimental autoimmune uveitis (EAU), a representative model for human AU, to investigate the effect of apremilast on regulating anti-inflammatory mediators. Our study demonstrated that apremilast treatment resulted in a decrease in vascular leakage, macular edema, and inflammatory cell infiltration in the retina, corresponding to decreased clinical and pathological scores. Specifically, apremilast decreased the proportion and population of Th17 cells and increased the proportion and population of T regulatory (Treg) cells. Mechanistically, apremilast may regulate Th17 and Treg cells by inhibiting the phosphorylation of the phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT)/Forkhead box O1 (FoxO1) signaling pathway. These findings suggested that apremilast alleviated EAU by regulating Th17 and Treg through the PI3K/AKT/FoxO1 pathway.

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Section: Discussionmentioning

confidence: 99%

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Chen

et al. 2020

Front. Immunol.

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“…FOXO1 has been implicated in a variety of cellular processes, such as apoptosis, proliferation, oxidative stress, and inflammation (Kandula et al, 2016). In recent years, FOXO1 has also been associated with tumor development and metabolic diseases, including obesity, diabetes, and atherosclerosis (Peng et al, 2020). The activation of FOXO1 is considered an attractive therapy towards cancers due to its tumor inhibition characteristics (Link, 2019).…”

Section: Discussionmentioning

confidence: 99%

miR‐221‐3p regulates apoptosis of ovarian granulosa cells via targeting FOXO1 in older women with diminished ovarian reserve (DOR)

Wei

Xiang

et al. 2021

Molecular Reproduction Devel

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In our earlier study, we showed that the expression of microRNA‐221‐3p (miR‐221‐3p) was significantly lower in women of advanced age with diminished ovarian reserve (DOR) compared with young women with normal ovarian reserve (NOR). Therefore, in this study, we aimed to explore how miR‐221‐3p regulates apoptosis of granulosa cells and the pathogenesis of DOR. Bioinformatics prediction and dual‐luciferase reporter assay were conducted to identify the target gene of miR‐221‐3p. miR‐221‐3p expression was manipulated by transfecting KGN cells with miR‐221‐3p mimics, inhibitor, and negative control. Following transfection, apoptosis of granulosa cells was determined by flow cytometry, and the expression of the target gene was measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis (WB). In addition, the expression of the target gene in granulosa cells of DOR patients and NOR patients was measured. miR‐221‐3p were found to directly bind the 3ʹ untranslated region of Forkhead box O1 (FOXO1). Transfection with miR‐221‐3p mimics significantly decreased the apoptosis rate of KGN cells compared with transfection with miR‐221‐3p inhibitors. The expression level of miR‐221‐3p was negatively correlated with the messenger RNA and protein levels of the FOXO1 gene. Besides, FOXO1 expression was upregulated in DOR patients. In conclusion, these results provide evidence that downregulation of miR‐221‐3p expression promotes apoptosis of granulosa cells by upregulating FOXO1 expression, thus serving an important role in DOR pathogenesis.

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“…In addition to TGF‐β1/Smad playing a role in the regulation of fibroblast proliferation and apoptosis, an increasing number of studies showed that the transcription factor forkhead box O1 (FoxO1) was also involved in the regulation of fibroblast proliferation and apoptosis 20 . FoxO1, as a multifunctional transcription factor, is closely related to cell apoptosis, proliferation, oxidative stress, energy metabolism, etc 21,22 Increased FoxO1 activity in diabetic mice 23 plays a key role in wound healing 24 . Therefore, regulating the effects of FoxO1 on cell proliferation and apoptosis is an important way to promote diabetic wound healing 25 …”

Section: Discussionmentioning

confidence: 99%

Ski promotes proliferation and inhibits apoptosis in fibroblasts under high‐glucose conditions via the FoxO1 pathway

et al. 2020

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A Review of FoxO1-Regulated Metabolic Diseases and Related Drug Discoveries

Cited by 88 publications

References 61 publications

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

miR‐221‐3p regulates apoptosis of ovarian granulosa cells via targeting FOXO1 in older women with diminished ovarian reserve (DOR)

Ski promotes proliferation and inhibits apoptosis in fibroblasts under high‐glucose conditions via the FoxO1 pathway

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