FOXO transcription factors in non-alcoholic fatty liver disease

Dong, X. Charlie

doi:10.1016/j.livres.2017.11.004

Cited by 38 publications

(38 citation statements)

References 71 publications

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“…The forkhead protein family comprises of more than 100 members in humans and are enumerated FOXA to FOXR based on their sequence similarity [ 104 ]. The members of the FOXO subfamily, which consists of FOXO1, FOXO3, FOXO4, and FOXO6, are regulated by insulin signaling whereby Akt-mediated phosphorylation sequesters FOXOs within the cytosol, inhibiting their transcriptional activity in the nucleus [ 105 ]. FOXO family members mediate the expression of genes that play a role in cell death, DNA repair, glucose, and energy metabolism [ 106 ].…”

Section: Glucose Metabolismmentioning

confidence: 99%

“…In addition, FOXO1 induces the transcription of genes involved in the hepatic assembly of VLDL, reducing hepatic steatosis [ 106 ]. The genetic ablation of FOXO increases susceptibility to NAFLD and NASH in mice [ 105 ]. Specifically, the deletion of FOXO1/3 or FOXO1/3/4 genes in mouse livers leads to mild or moderate hepatic steatosis, even when mice are maintained on a regular chow diet [ 105 ].…”

Section: Glucose Metabolismmentioning

confidence: 99%

“…The genetic ablation of FOXO increases susceptibility to NAFLD and NASH in mice [ 105 ]. Specifically, the deletion of FOXO1/3 or FOXO1/3/4 genes in mouse livers leads to mild or moderate hepatic steatosis, even when mice are maintained on a regular chow diet [ 105 ]. Exposing the mice to HFD supplemented with cholesterol further exacerbates steatosis in FOXO1/3/4-deficient mice [ 105 ].…”

Section: Glucose Metabolismmentioning

confidence: 99%

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Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

2020

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Obesity is the primary risk factor for the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the worldwide prevalence of which continues to increase dramatically. The liver plays a pivotal role in the maintenance of whole-body lipid and glucose homeostasis. This is mainly mediated by the transcriptional activation of hepatic pathways that promote glucose and lipid production or utilization in response to the nutritional state of the body. However, in the setting of chronic excessive nutrition, the dysregulation of hepatic transcriptional machinery promotes lipid accumulation, inflammation, metabolic stress, and fibrosis, which culminate in NAFLD. In this review, we provide our current understanding of the transcription factors that have been linked to the pathogenesis and progression of NAFLD. Using publicly available transcriptomic data, we outline the altered activity of transcription factors among humans with NAFLD. By expanding this analysis to common experimental mouse models of NAFLD, we outline the relevance of mouse models to the human pathophysiology at the transcriptional level.

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Section: Glucose Metabolismmentioning

confidence: 99%

Section: Glucose Metabolismmentioning

confidence: 99%

Section: Glucose Metabolismmentioning

confidence: 99%

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Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

2020

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“…In addition, the expression level of the transcription factor Forkhead box protein O1 (FOXO1) was investigated. This transcriptional factor plays key roles in different physiological processes, including fibrosis, wound healing, glucose metabolism, tissue repair and oxidative stress controlling (Ponugoti et al, ; Mori et al, ; Dong, ), and several studies have pointed its phosphorylation by the AKT, which translocates the protein to the cytoplasm (Massagué et al, ; Adachi et al, ; Verano‐Braga et al, ). Moreover, FOXO1 is able to interact with TGF‐β/ SMAD signaling in a close interconnected feedback (Luo, ).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‐1254 contributes to the controlling of pro‐fibrogenic environment in LX‐2 cells by modulating SMAD3 and wound repair: new insights in hepatic fibrosis

Gonçalves

Silva

Scarinci

et al. 2019

Cell Biology International

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Hepatic fibrosis and its end‐stage cirrhosis have increased worldwide, and, despite all the efforts, no successful therapy is available. More recently, the heptapeptide angiotensin‐(1‐7) [ang‐(1‐7)] was reported to be able to modulate liver fibrosis and even steatosis; however, the molecular bases of these effects are not clear. In this study, we investigated the overexpression of the microRNA‐1254 in the human hepatic stellate cell line LX‐2, based on the effect of the heptapeptide in such cells, previously, demonstrated by our research group. In addition, this miRNA was chosen based on the identification of putative binding site of this small molecule in the mRNA sequences of different molecular connectors of the AKT/ PI3K pathway, which is modulated by the heptapeptide and connects to the control of several cellular mechanisms, including proliferation, survival, migration, and even liver fibrogenesis. The results revealed an innovative function of the miR‐1254 in controlling SMAD3 and pro‐fibrosing elements as well as the wound healing response in LX‐2, attenuating the scaring repair of the injured tissue. The combined findings provide useful information for future studies on the controlling of hepatic fibrogenesis.

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“…FoxO, a key downstream regulator in the PI3K-Akt signaling pathway belonging to subclass of the forkhead proteins family, regulates metabolic homeostasis in response to oxidative stress. Moreover, oxidative stress resistance, apoptosis, and glucose metabolism were also modulated by FoxO [44]. Importantly, FoxO transcription factors benefit liver fibrosis through inhibiting proliferation and transdifferentiation of HSCs [45].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

Tao

Tian

Chen

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

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FOXO transcription factors in non-alcoholic fatty liver disease

Cited by 38 publications

References 71 publications

Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

MicroRNA‐1254 contributes to the controlling of pro‐fibrogenic environment in LX‐2 cells by modulating SMAD3 and wound repair: new insights in hepatic fibrosis

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

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