Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis

Wang, Yan; Jiang, Xiaoyu; Liu, Li; Jiang, Hui‐Qing

doi:10.3748/wjg.14.5186

Cited by 29 publications

(25 citation statements)

References 18 publications

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“…In a microarray study of human HSCs, cells became senescent and switched from a primarily fibrogenic to an inflammatory phenotype, with decreased proliferation and gene expression, and increased apoptosis28. PI3K/AKT as the upstream of the mTOR signaling pathway, inhibition of PI3K/Akt signaling pathway has been shown to induce HSCs apoptosis and attenuate liver fibrosis in vitro 29. These findings suggest that reduced myofibroblast proliferation and increased myofibroblast apoptosis could effectively reduce fibrosis.…”

Section: Discussionmentioning

confidence: 94%

mTOR Overactivation in Mesenchymal cells Aggravates CCl4− Induced liver Fibrosis

Shan

Ding

et al. 2016

Sci Rep

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Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl4, oil or CCl4+ rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl4− induced liver fibrosis and the rapamycin prevent its occurance.

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Section: Discussionmentioning

confidence: 94%

mTOR Overactivation in Mesenchymal cells Aggravates CCl4− Induced liver Fibrosis

Shan

Ding

et al. 2016

Sci Rep

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“…Both adherent and floating cells were harvested for the apoptosis assay by using the Annexin-V/propidium iodide double-labeled flow cytometry kit (Baosai, Beijing, China) as previously described [10]. Cells were analyzed by flow cytometry with a Becton Dickinson FACS-420 flow cytometer (Franklin Lakes, NJ, USA).…”

Section: Apoptosis Analysis Of Hscsmentioning

confidence: 99%

“…Cells were treated as described above and harvested for morphological examination via transmission electron microscopy (TEM) evaluation as previously described [10].…”

Section: Apoptosis Analysis Of Hscsmentioning

confidence: 99%

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New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis

Wang

Gao

Zhang

et al. 2010

Journal of Hepatology

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220

152

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“…Apoptosis of T and B-lymphocytes were found inhibited in transgenic mice that overexpressed active Akt (Bommhardt et al 2004). Conversely, inhibition of PI3K-Akt signaling pathway induced apoptosis in rat hepatic stellate cells, even under strong mitotic stimulation by platelet-derived growth factor (Wang et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Indoor Air Pollution from Biomass Burning Activates Akt in Airway Cells and Peripheral Blood Lymphocytes

et al. 2010

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Biomass burning is a major source of indoor air pollution in rural India. The authors investigated in this study whether cumulative exposures to biomass smoke cause activation of the serine/threonine kinase Akt in airway cells and peripheral blood lymphocytes (PBL). For this, the authors enrolled 87 premenopausal (median age 34 years), nonsmoking women who used to cook with biomass (wood, dung, crop wastes) and 85 agematched control women who cooked with cleaner fuel liquefied petroleum gas. Immunocytochemical and immunoblotting assays revealed significantly higher levels of phosphorylated forms of Akt protein (p-Akt ser473 and p-Akt thr308 ) in PBL, airway epithelial cells, alveolar macrophages, and neutrophils in sputum of biomass-using women than control. Akt activation in biomass users was associated with marked rise in generation of reactive oxygen species and concomitant depletion of superoxide dismutase. Measurement of particulate matter having a diameter of less than 10 and 2.5 mm in indoor air by real-time aerosol monitor showed 2 to 4 times more particulate pollution in biomass-using households, and Akt activation was positively associated with particulate pollution after controlling potential confounders. The findings suggest that chronic exposure to biomass smoke activates Akt, possibly via generation of oxidative stress.

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Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis

Abstract: Inhibition of PI 3-K/Akt signaling pathway induces apoptosis in HSC.

Cited by 29 publications

References 18 publications

mTOR Overactivation in Mesenchymal cells Aggravates CCl4− Induced liver Fibrosis

mTOR Overactivation in Mesenchymal cells Aggravates CCl4− Induced liver Fibrosis

New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis

Indoor Air Pollution from Biomass Burning Activates Akt in Airway Cells and Peripheral Blood Lymphocytes

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