Activation of FoxO3a/Bim axis in patients with Primary Biliary Cirrhosis

Kopycińska, Justyna; Kempińska-Podhorodecka, Agnieszka; Haas, Tara L.; Elias, Elwyn; DePinho, Ronald A.; Paik, Jihye; Milkiewicz, Piotr; Milkiewicz, Małgorzata

doi:10.1111/liv.12030

Cited by 22 publications

(17 citation statements)

References 36 publications

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“…ER stress activates Nrf2 and ATF6, both of which regulate the orphan nuclear receptor, Shp (small heterodimer partner) which acts as a transcriptional corepressor modulating cyclin D1 and subsequent hepatic tumorigenesis [106, 107]. The ER stress sensor PERK has been shown to phosphorylate the Forkhead transcription factor 3 (FOXO3) [108] and suppressed FOXO3 exacerbates alcoholic hepatitis and insulin resistance impairing cyclin D function promoting HCC [109–111]. Thus, abnormal functions of cyclin D under ER stress conditions most likely disturb liver cell proliferation (Figure 2).…”

Section: Emerging Role Of Aerr In Liver Tumorigenesis and Hccmentioning

confidence: 99%

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

Cheng

2014

International Journal of Hepatology

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Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also in vivo in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

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Section: Emerging Role Of Aerr In Liver Tumorigenesis and Hccmentioning

confidence: 99%

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

Cheng

2014

International Journal of Hepatology

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“…In a complementary study, it was determined that approximately 11% of CCCTC-binding factor (CTCF) binding sites were allele-specific in cell lines derived from parents and children from two ancestries [57]. Two are the transcription factor particularly upregulated in PBC: transcription initiation factor 250 KDa subunit (TAFII-250) and PAX3/forkhead transcription factor [58,59]. Recently, SMARC1 [60] a transcription regulator that modulates the chromatin structure and is involved in apoptosis, DNA damage, and differentiation, was observed as hypermethylated in PBC patients.…”

Section: Introductionmentioning

confidence: 99%

The epigenetics of PBC: The link between genetic susceptibility and environment

Marzorati

Lleo

Carbone

et al. 2016

Clinics and Research in Hepatology and Gastroenterology

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“…1, 2, 3, 4, 5, 6 Genetic variability is interacted with environmental factors, which makes liver damage in a variety of severity. 7 In the damaged liver, cell death modes include apoptosis, necrosis, necroptosis, and autophagy.…”

Section: Introduction Of Hepatic Apoptosismentioning

confidence: 99%

Molecular mechanisms of hepatic apoptosis

2014

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Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis.

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Activation of FoxO3a/Bim axis in patients with Primary Biliary Cirrhosis

Abstract: Our results imply that the FoxO3/Bim signalling pathway can be of importance in the livers of patients with PBC.

Cited by 22 publications

References 36 publications

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

The epigenetics of PBC: The link between genetic susceptibility and environment

Molecular mechanisms of hepatic apoptosis

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