Hepatocyte Autophagy: Maintaining a Toxic‐Free Environment

Francis, Heather; Wu, Nan; Alpini, Gianfranco; Meng, Fanyin

doi:10.1002/hep.31219

Cited by 6 publications

(9 citation statements)

References 11 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Research indicates that hepatocyte autophagy can maintain a dynamic cell balance and ensure energy supply . However, our results in vivo showed that G-Rg2 significantly inhibited the autophagy of the whole liver in CDAHFD-fed mice (Figure ), which conflicts with previous reports.…”

Section: Resultscontrasting

confidence: 99%

“…Research indicates that hepatocyte autophagy can maintain a dynamic cell balance and ensure energy supply. 12 However, our results in vivo showed that G-Rg2 significantly inhibited the autophagy of the whole liver in CDAHFD-fed mice (Figure 4), which conflicts with previous reports. Therefore, to eliminate the effects of G-Rg2 on hepatocyte autophagy, we used OA to simulate in vivo the cell damage caused by lipid accumulation due to CDAHFD and to further explore the effect of G-Rg2 on hepatocyte autophagy.…”

Section: ■ Resultscontrasting

confidence: 99%

“…In recent years, evidence has increasingly shown that this process contributes to liver fibrosis, , albeit with opposing functions in different cells . In hepatocytes, autophagy can maintain the protein, lipid, and organelle homeostasis in the liver but can also cause damage that can lead to liver injury . Studies indicate that hepatocyte injury can increase TGF-β1 production, − which promotes hepatic stellate cell (HSC) activation and accelerates liver fibrosis .…”

Section: Introductionmentioning

confidence: 99%

“…11 In hepatocytes, autophagy can maintain the protein, lipid, and organelle homeostasis in the liver but can also cause damage that can lead to liver injury. 12 Studies indicate that hepatocyte injury can increase TGF-β1 production, 13−15 which promotes hepatic stellate cell (HSC) activation and accelerates liver fibrosis. 16 By contrast, autophagy in HSCs provides energy for their activation by mediating stored lipid droplet degradation.…”

Section: ■ Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ginsenoside Rg2 Ameliorating CDAHFD-Induced Hepatic Fibrosis by Regulating AKT/mTOR-Mediated Autophagy

Chen

Pan

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

Ginsenoside Rg2 (G-Rg2) in the rhizome of Panax ginseng can modify lipid accumulation, oxidative stress, and apoptosis in the liver induced by a high-fat diet. This research adds to this by assessing the potential antifibrosis effect of G-Rg2 (including possible mechanisms). G-Rg2 significantly improved pathological changes in liver tissue induced by a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD), it inhibited serum transaminase, plasma lipopolysaccharide, and liver hydroxyproline levels; it inhibited TGF-β1, α-SMA, and COL1A1 expression, it activated the AKT/mTOR signal pathway, and it inhibited liver expression of autophagy-related proteins. The in vitro experiments showed that G-Rg2 also restored the autophagy flux impairment induced by oleic acid and inhibited TGF-β1 expression by promoting p62 degradation in hepatocytes. In hepatic stellate (HSC-T6) cells, G-Rg2 reversed lipopolysaccharide-induced activation through the AKT/mTOR signaling pathway, inhibiting autophagy. Thus, G-Rg2 ameliorates CDAHFD-induced liver fibrosis and lipopolysaccharide-induced HSC-T6 cell activation by inhibiting AKT/mTOR-mediated autophagy.

show abstract

Section: Resultscontrasting

confidence: 99%

Section: ■ Resultscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ginsenoside Rg2 Ameliorating CDAHFD-Induced Hepatic Fibrosis by Regulating AKT/mTOR-Mediated Autophagy

Chen

Pan

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…Её утрата усугубляет фиброз печени за счет снижения внутрипеченочного оксида азота (NO) и измененного ответа на окислительный стресс [34]. В гепатоцитах аутофагия необходима для сохранения гомеостаза печени, связанного с белками, липидами и органеллами, а нарушение её регуляции приводит к повреждению, воспалению, фибро-и онкогенезу [35]. Y. Shen Y. и соавт.…”

Section: Reviewunclassified

Molecular stimuli of fibrogenic activation in hepatic stellate cells

Гарбузенко¹

2022

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

View full text Add to dashboard Cite

Цель обзора - оценка роли молекулярных стимулов фиброгенной активации звёздчатых клеток печени (ЗКП), играющих важную роль в печёночном фиброгенезе. Показано, что для переформатирования неподвижных ЗКП в активированный миофибробластоподобный фенотип требуется изменение экспрессии нескольких сотен различных генов. Ряд стимулирующих факторов способны влиять на рецепторы для множества паракринных и аутокринных индукторов этого процесса. Возможными ключевыми регуляторами активации ЗКП являются мультидоменная сигнальная молекула GIV/Girdin и метил-CpG-связывающий белок 2 (MеCP2). Кроме того, их трансдифференцировка может быть обусловлена эпигенетическими механизмами, которые включают метилирование ДНК и модификации гистонов, и контролируются многочисленными некодирующими РНК. Сохранять экспансию и профиброгенную активность ЗКП при постоянном воздействии агрессивного агента способно устойчивое увеличение сигнальной трансдукции hedgehog (Hh). Содействует печёночному фиброгенезу и аутофагия в ЗКП. Под влиянием молекулярных стимулов ЗКП вступают в клеточный цикл и проходят фазу начальной, а затем устойчивой активации. В это время происходят многочисленные изменения в транскрипции генов коллагена I типа, α-гладкомышечного актина (α-SMA), трансформирующего фактора роста (TGF)-β1 и его рецепторов, матриксной металлопротеиназы (ММП)-2, тканевых ингибиторов матриксных металлопротеиназ (ТИМП)-1 и 2, чему способствуют отсутствующие в неподвижных ЗКП транскрипционные факторы Ets-1, Mef2, CREB, Egr-1, JunD, рецептор витамина D, CCAAT/энхансер-связывающий белок β (C/EBP-β) и другие. Понимание патофизиологических механизмов активации ЗКП является чрезвычайно важным для разработки таргетной антифибротической терапии. Внедрение её в клиническую практику позволит улучшить прогноз при хронических заболеваниях печени и повысить качество жизни пациентов. The aim of this review was to describe the molecular stimuli of fibrogenic activation in hepatic stellate cells (HSCs), which play an important role in hepatic fibrogenesis. It has been established that the transformation of quiescent HSCs into activated, myofibroblast-like phenotypes requires changes in the expression of several hundred different genes. A number of stimulating factors is able to influence the receptors for a variety of paracrine and autocrine inducers of this process. Possible key regulators of HSCs activation are the multidomain signaling molecules GIV/Girdin and methyl-CpG-binding protein 2 (MеCP2). In addition, their transdifferentiation may be due to epigenetic mechanisms, which include DNA methylation and histone modifications, and are controlled by numerous non-coding RNAs (ncRNAs). A steady increase in the hedgehog (Hh) signal transduction is able to maintain the expansion and pro-fibrogenic activity of HSCs with constant exposure to an aggressive agent. The HSC autophagy also contributes to hepatic fibrogenesis. Under the influence of molecular stimuli, HSCs enter the cell cycle and undergo phases of initial and then perpetual activation. At this time, there are numerous changes in the transcription of genes of type I collagen, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1 and its receptors, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2. This is facilitated by transcription factors that are absent in quiescent HSCs, such as Ets-1, Mef2, CREB, Egr-1, JunD, vitamin D receptor, CCAAT/enhancer-binding protein β (C/EBP-β), etc. Understanding the pathophysiological mechanisms of HSC activation is extremely important for the development of targeted antifibrotic therapy. Its introduction into clinical practice will improve the prognosis for chronic liver diseases and enhance the quality of life of such patients.

show abstract

Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy

Zhang

Cheng

et al. 2023

Pharmacology

View full text Add to dashboard Cite

Background: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer. It is also involved in chemotherapy resistance by a dual role, since it not only promotes the occurrence of drug resistance but also reverses it. Previous findings suggest that the regulation of autophagy can be used as an effective strategy in tumor therapy. Summary: Recent studies found that small molecules from natural products and their derivatives exert anticancer activity by regulating the level of autophagy in tumor cells. Key Messages: Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy.

show abstract

Hepatocyte Autophagy: Maintaining a Toxic‐Free Environment

Cited by 6 publications

References 11 publications

Ginsenoside Rg2 Ameliorating CDAHFD-Induced Hepatic Fibrosis by Regulating AKT/mTOR-Mediated Autophagy

Ginsenoside Rg2 Ameliorating CDAHFD-Induced Hepatic Fibrosis by Regulating AKT/mTOR-Mediated Autophagy

Molecular stimuli of fibrogenic activation in hepatic stellate cells

Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy

Contact Info

Product

Resources

About