Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (25 February 2021) | Viewed by 22270

Share This Special Issue

Special Issue Editors

Dr. Jae Kyeom Kim

E-Mail Website
Guest Editor

Department of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE, USA
Interests: metabolism of carcinogens, toxicology, multi-omics approaches to nutrition research, carcinogenesis

Dr. Jin Hyup Lee

E-Mail Website
Guest Editor

Department of Food and Biotechnology, Korea University, Sejong, Korea
Interests: redox biology; translational medicine; mitochondria; apoptosis; signal transduction; natural compounds

Special Issue Information

Dear Colleagues,

The liver possesses diverse functions and is a critical organ for metabolizing both endogenous and exogenous constituents. Liver diseases encompass an array of conditions such as hepatitis, non-alcoholic fatty liver disease, and cirrhosis. Multiple risk factors have been identified for different liver diseases; these risk factors can be inherited (genetic factors) and/or acquired from environments (e.g., alcohol, viruses). Depending upon degree, progress of diseases, and individual conditions, liver diseases can lead to irreversible, life-threatening situations. In contrast, effective treatments and/or prevention would provide a better chance to mitigate detrimental consequences in which evidence-based guidance in practice is essential. This Special Issue therefore aims to collect the most leading-edge updates related to the topic. The topics relevant to the Issue include the broadest aspects of liver disease pathophysiology, therapeutic and preventive mechanisms against the diseases, and underlying molecular mechanisms.

Dr. Jae Kyeom Kim
Dr. Jin Hyup Lee
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

liver cell death
biomarkers of liver diseases
trends in liver disease therapy
hepatocellular carcinoma
reactive oxygen species
lipid metabolism
xenobiotic metabolism
inflammation
Kupffer and Hepatic stellate cells
gut–liver axis
microbiome

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

14 pages, 1849 KiB

Open AccessArticle

Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

by Rok Razpotnik, Petra Nassib, Tanja Kunej, Damjana Rozman and Tadeja Režen

Int. J. Mol. Sci. 2021, 22(14), 7477; https://doi.org/10.3390/ijms22147477 - 12 Jul 2021

Cited by 5 | Viewed by 2655

Abstract

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression. Full article

(This article belongs to the Special Issue Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention)

► Show Figures

Figure 1

15 pages, 4854 KiB

Open AccessArticle

Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl₄ and TAA-Induced Liver Fibrosis in Mice

by Yi-Jen Liao, Yuan-Hsi Wang, Chien-Ying Wu, Fang-Yu Hsu, Chia-Ying Chien and Yi-Chieh Lee

Int. J. Mol. Sci. 2021, 22(6), 2934; https://doi.org/10.3390/ijms22062934 - 13 Mar 2021

Cited by 14 | Viewed by 5467

Abstract

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer’s disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, β-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl₄)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-β (TGF-β)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl₄-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment. Full article

(This article belongs to the Special Issue Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention)

► Show Figures

Figure 1

13 pages, 2296 KiB

Open AccessArticle

Formyl Peptide Receptor 2 Alleviates Hepatic Fibrosis in Liver Cirrhosis by Vascular Remodeling

by Ji Hye Jun, Soo Young Park, Sohae Park, Hee Jung Park, Jae Yeon Kim, Gyu Tae Park, Si Hyun Bae, Jae Ho Kim and Gi Jin Kim

Int. J. Mol. Sci. 2021, 22(4), 2107; https://doi.org/10.3390/ijms22042107 - 20 Feb 2021

Cited by 12 | Viewed by 2663

Abstract

Hexapeptide WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met), a ligand of formyl peptide receptor 2, exhibits anti-inflammatory and angiogenic properties in disease models. However, the therapeutic effects of WKYMVm on hepatic fibrosis have not been evaluated to date. Therefore, we investigated whether WKYMVm exerts antifibrotic effects and induces vascular regeneration in a rat model of bile duct ligation (BDL). The antifibrotic and angiogenic effects of WKYMVm on liver regeneration in the BDL rat model were analyzed using biochemical assays, qRT-PCR, western blotting, immunofluorescence, and immunohistochemistry. To determine the effects of WKYMVm on hepatic fibrosis and angiogenesis in vitro, we measured the expression levels of fibrotic factors in hepatic stellate cells (HSCs) and angiogenic factors in human umbilical vein endothelial cells (HUVECs). WKYMVm attenuated the expression of collagen type I (Col I) and α-smooth muscle actin (α-SMA) and significantly increased the levels of angiogenetic factors in the BDL model (p < 0.05). WKYMVm reduced fibrotic marker expression in transforming growth factor (TGF)-β-induced HSCs and promoted angiogenic activity through tube formation in 5-Fluorouracil (FU)-treated HUVECs (p < 0.05). Also, WKYMVm administration enhanced hepatocyte proliferation in BDL rats (p < 0.05). The WKYMVm alleviates hepatic fibrosis by inhibiting HSC activation and promotes hepatic regeneration via vascular remodeling. These data suggest that the WKYMVm may be a new therapeutic agent for liver fibrosis. Full article

(This article belongs to the Special Issue Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention)

► Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1311 KiB

Open AccessReview

A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

by Marinela Krizanac, Paola Berenice Mass Sanchez, Ralf Weiskirchen and Anastasia Asimakopoulos

Int. J. Mol. Sci. 2021, 22(6), 2865; https://doi.org/10.3390/ijms22062865 - 11 Mar 2021

Cited by 10 | Viewed by 3905

Abstract

Excess calorie intake and a sedentary lifestyle have made non-alcoholic fatty liver disease (NAFLD) one of the fastest growing forms of liver disease of the modern world. It is characterized by abnormal accumulation of fat in the liver and can range from simple steatosis and non-alcoholic steatohepatitis (NASH) to cirrhosis as well as development of hepatocellular carcinoma (HCC). Biopsy is the golden standard for the diagnosis and differentiation of all NAFLD stages, but its invasiveness poses a risk for patients, which is why new, non-invasive ways of diagnostics ought to be discovered. Lipocalin-2 (LCN2), which is a part of the lipocalin transport protein family, is a protein formally known for its role in iron transport and in inflammatory response. However, in recent years, its implication in the pathogenesis of NAFLD has become apparent. LCN2 shows significant upregulation in several benign and malignant liver diseases, making it a good candidate for the NAFLD biomarker or even a therapeutic target. What makes LCN2 more interesting to study is the fact that it is overexpressed in HCC development induced by chronic NASH, which is one of the primary causes of cancer-related deaths. However, to this day, neither its role as a biomarker for NAFLD nor the molecular mechanisms of its implication in NAFLD pathogenesis have been completely elucidated. This review aims to gather and closely dissect the current knowledge about, sometimes conflicting, evidence on LCN2 as a biomarker for NAFLD, its involvement in NAFLD, and NAFLD-HCC related pathogenesis, while comparing it to the findings in similar pathologies. Full article

(This article belongs to the Special Issue Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention)

► Show Figures

Figure 1

26 pages, 1846 KiB

Open AccessReview

DNA Methylation in Nonalcoholic Fatty Liver Disease

by Jeongeun Hyun and Youngmi Jung

Int. J. Mol. Sci. 2020, 21(21), 8138; https://doi.org/10.3390/ijms21218138 - 30 Oct 2020

Cited by 58 | Viewed by 6532

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a widespread hepatic disorder in the United States and other Westernized countries. Nonalcoholic steatohepatitis (NASH), an advanced stage of NAFLD, can progress to end-stage liver disease, including cirrhosis and liver cancer. Poor understanding of mechanisms underlying NAFLD progression from simple steatosis to NASH has limited the development of effective therapies and biomarkers. An accumulating body of studies has suggested the importance of DNA methylation, which plays pivotal roles in NAFLD pathogenesis. DNA methylation signatures that can affect gene expression are influenced by environmental and lifestyle experiences such as diet, obesity, and physical activity and are reversible. Hence, DNA methylation signatures and modifiers in NAFLD may provide the basis for developing biomarkers indicating the onset and progression of NAFLD and therapeutics for NAFLD. Herein, we review an update on the recent findings in DNA methylation signatures and their roles in the pathogenesis of NAFLD and broaden people’s perspectives on potential DNA methylation-related treatments and biomarkers for NAFLD. Full article

(This article belongs to the Special Issue Liver Diseases: Causes, Molecular Mechanisms and Treatment/Prevention)

► Show Figures