Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

Katrinli, Şeyma; Özdil, Kamil; Şahin, Abdurrahman; Öztürk, Oğuzhan; Kır, Gözde; Baykal, Ahmet Tarık; Akgun, Emel; Saraç, Ömer; Sokmen, Mehmet; Doganay, Levent; Doğanay, Gizem Dinler

doi:10.1186/s12953-017-0114-4

Cited by 20 publications

(12 citation statements)

References 48 publications

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“…For instance, the randomness of HBV DNA integration events in the host genome adds to the heterogeneity of HBV-related HCC[ 108 ]. Cirrhosis and HCC typically occur more than 20 years after the initial infection[ 109 ]. Smoking, alcohol consumption, aflatoxin exposure, obesity, diabetes, and treatment interventions during this period are strong confounders that also lead to clinical heterogeneity[ 110 ].…”

Section: Discussionmentioning

confidence: 99%

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Akçay

Katrinli

Özdil

et al. 2018

WJG

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The clinical outcome of hepatitis B virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure, depending on the success or failure of immune response to HBV. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

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Section: Discussionmentioning

confidence: 99%

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Akçay

Katrinli

Özdil

et al. 2018

WJG

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“…The results of the present study also demonstrated the negative association between PBLD and HCC. Although a number of studies have indicated that PBLD may be involved in HCC progression, the mechanism is unknown (10,20). Additionally, to the best of our knowledge, no effective PBLD activator has been identified.…”

Section: Discussionmentioning

confidence: 99%

Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1

Wu¹,

Niu²,

Yuan³

et al. 2019

Exp Ther Med

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Although it is known that Phenazine biosynthesis-like domain-containing protein (PBLD) expression is downregulated in hepatocellular carcinoma (HCC), its biological function is unclear. Additionally, no agents capable of upregulating PBLD exist. In the current study, the relationship between PBLD and HCC was analyzed using clinicopathological specimens. A HCC cell model, microarray analysis and an animal model were used to verify the therapeutic effect of cedrelone on HCC. The present study demonstrated that PBLD inhibited HCC progression. Furthermore, the present study revealed that cedrelone possessed treated-HCC capabilities via targeted PBLD overexpression. The epithelial-mesenchymal transition phenotype and growth rate were inhibited and the apoptosis ratio was promoted by cedrelone following PBLD overexpression. The Ras and Ras-proximate-1 signaling pathways were also determined to be regulated by cedrelone via PBLD activation in HCC. PBLD may therefore be an independent predictor of HCC progression and a novel target for HCC treatment. Additionally, the PBLD activator, cedrelone, may be a potential drug for HCC treatment in the future.

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“…Unsurprisingly, changes in metabolic process in proteome level were observed. For glucose metabolism, enzymes for glycolysis (hexokinase‐1, hexokinase‐2,6‐phosphofructokinase, aldolase A, phosphoglycerate mutase, and PKM) in the cytoplasm were up‐regulated, and PKM as a potential new therapeutic target and biomarker were found in proteomic profiling of HBV‐infected liver biopsy tissues with different fibrotic stages . Liver injury accelerated glycogenolysis .…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

Liu

Dai

et al. 2017

Proteomics

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Liver fibrosis is a common pathological feature of many chronic liver diseases. To characterize the entire panorama of proteome changes in dimethylnitrosamine (DMN)-induced liver fibrosis, isobaric tags for relative and absolute quantitation (iTRAQ)-based differential proteomic analysis is performed with DMN-induced liver fibrosis rats. A total of 4155 confidently identified proteins are found, with 365 proteins showing significant changes (fold changes of >1.5 or < 0.67, p < 0.05). In metabolic activation, proteins assigned to drug metabolism enzymes (e.g., CYP2D1) change, suggesting that the liver protection mechanism is activated to relieve DMN toxicity. In addition, the altered proteins of immune response and oxidative stress may activate hepatic stellate cells. Glucose metabolism disorder in DMN model rats is demonstrated by a decrease in key enzymes (e.g., ACSL1) in fatty acid metabolism, a tricabolic acid cycle-related enzyme (SDH), glycogenolysis enzyme, and gluconeogenesis enzymes (PC, PCKGC) and by an increase in glycolysis enzymes (e.g., HXK1). Meanwhile, alterations in iron and calcium ion homeostasis proteins are observed. Our results also show that mitochondrial dysfunction may be involved in DMN hepatotoxicity. In conclusion, these altered liver proteins in the DMN model and control rats provide data for understanding the functional mechanism of liver fibrosis.

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Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

Cited by 20 publications

References 48 publications

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies

Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

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