Hepatitis B virus induces expression of cholesterol metabolism-related genes<i>via</i>TLR2 in HepG2 cells

Li, Yingju

doi:10.3748/wjg.v19.i14.2262

Cited by 36 publications

(30 citation statements)

References 29 publications

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“…We considered this cellular cholesterol overload as the key driver of ACAT stimulation [44] leading to the esterification of free cholesterol excess into intracellular cholesterol pools (lipid droplet accumulation) and decreased the amount of plasma membrane free cholesterol, diminishing the free cholesterol gradient requested for passive diffusion, a key macrophage cholesterol efflux regulator in normolipidemic conditions [36]. Our observations are in line with previous observations demonstrating that TLR4 and TLR2 agonists can upregulate SREBP2, HMGCR, and LDL-R expression and promote foam cell formation independently of oxidized-LDL uptake [29,45,46].…”

Section: Discussionsupporting

confidence: 89%

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Pagano

Magenta

D'agostino

et al. 2019

JCM

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Aims: Anti-Apolipoprotein A-1 autoantibodies (anti-ApoA-1 IgG) promote atherogenesis via innate immune receptors, and may impair cellular cholesterol homeostasis (CH). We explored the presence of anti-ApoA-1 IgG in children (5–15 years old) with or without familial hypercholesterolemia (FH), analyzing their association with lipid profiles, and studied their in vitro effects on foam cell formation, gene regulation, and their functional impact on cholesterol passive diffusion (PD). Methods: Anti-ApoA-1 IgG and lipid profiles were measured on 29 FH and 25 healthy children. The impact of anti-ApoA-1 IgG on key CH regulators (SREBP2, HMGCR, LDL-R, ABCA1, and miR-33a) and foam cell formation detected by Oil Red O staining were assessed using human monocyte-derived macrophages. PD experiments were performed using a validated THP-1 macrophage model. Results: Prevalence of high anti-ApoA-1 IgG levels (seropositivity) was about 38% in both study groups. FH children seropositive for anti-ApoA-1 IgG had significant lower total cholesterol LDL and miR-33a levels than those who were seronegative. On macrophages, anti-ApoA-1 IgG induced foam cell formation in a toll-like receptor (TLR) 2/4-dependent manner, accompanied by NF-kB- and AP1-dependent increases of SREBP-2, LDL-R, and HMGCR. Despite increased ABCA1 and decreased mature miR-33a expression, the increased ACAT activity decreased membrane free cholesterol, functionally culminating to PD inhibition. Conclusions: Anti-ApoA-1 IgG seropositivity is frequent in children, unrelated to FH, and paradoxically associated with a favorable lipid profile. In vitro, anti-ApoA-1 IgG induced foam cell formation through a complex interplay between innate immune receptors and key cholesterol homeostasis regulators, functionally impairing the PD cholesterol efflux capacity of macrophages.

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Section: Discussionsupporting

confidence: 89%

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Pagano

Magenta

D'agostino

et al. 2019

JCM

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“…These modifi cations cause triglycerides to accumulate in the hepatocyte 30 . A recent experimental study revealed that adenovirus containing the HBV genome (Ad-HBV) up-regulated the expression of genes related to cholesterol metabolism in HepG2 cells 31 , suggesting that HBV itself infl uences cholesterol metabolism. Nevertheless, the lipid profi les among individuals with chronic HBV remain a matter of debate in the literature.…”

Section: Discussionmentioning

confidence: 99%

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Nau

Soares

Shiozawa

et al. 2014

Rev. Soc. Bras. Med. Trop.

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“…In addition, HBV infection may alter hepatic cholesterol metabolism. HBV‐transfected HepG2 cells exhibited increased expression of low‐density lipoprotein receptor and 3‐hydroxy‐3‐methylglutharyl‐coenzyme A reductase (HMGCR) . In addition, a study in HBV‐infected humanized mice also revealed enhanced gene expression related to hepatic cholesterol production and uptake, including those encoding SREBP‐2, HMGCR and LDL receptor .…”

Section: Possible Mechanistic Role Of Hbv Infection In Nafld Pathogenmentioning

confidence: 99%

“…of low-density lipoprotein receptor and 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR). 94 In addition, a study in HBV-infected humanized mice also revealed enhanced gene expression related to hepatic cholesterol production and uptake, including those encoding SREBP-2, HMGCR and LDL receptor. 95 Further investigation identified the pre-S1 domain of the HBV envelope as the primary contributor to this phenomenon.…”

Section: Olism Hbv-transfected Hepg2 Cells Exhibited Increased Exprementioning

confidence: 99%

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

Zhang

Lin

Jiang

et al. 2020

Liver International

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Despite the widespread use of vaccines and antiviral drugs, approximately 350‐400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non‐alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.

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Hepatitis B virus induces expression of cholesterol metabolism-related genesviaTLR2 in HepG2 cells

Abstract: Ad-HBV increases LDLR and HMGCoAr expression, resulting in exacerbated cholesterol accumulation in HepG2 cells, which was mediated via the TLR2 pathway.

Cited by 36 publications

References 29 publications

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

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