Hepatic miR-29ab1 expression modulates chronic hepatic injury

Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl4) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of Lactobacillus, Bacteroides, and Akkermansia and decreased the relative abundance of Ralstonia, Alloprevotella, and Lachnoclostridium. However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.

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Exosomal miR-500 Derived From Lipopolysaccharide-Treated Macrophage Accelerates Liver Fibrosis by Suppressing MFN2

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.716209 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lisha Chen ◽

Yan Huang ◽

Zhixi Duan ◽

Peiqi Huang ◽

Hongbing Yao ◽

...

Keyword(s):

Liver Fibrosis ◽

Liver Cancer ◽

Mouse Model ◽

Immune Cells ◽

Hepatic Injury ◽

Stellate Cell ◽

Activated Macrophages ◽

Hepatic Macrophages ◽

Chronic Hepatic Injury ◽

Serum Exosomes

Liver fibrosis is an outcome of chronic hepatic injury, which can eventually result in cirrhosis, liver failure, and even liver cancer. The activation of hepatic stellate cell (HSC) is a prominent driver of liver fibrosis. Recently, it has been found that the crosstalk between HSCs and immune cells, including hepatic macrophages, plays an important role in the initiation and development of liver fibrosis. As a vital vehicle of intercellular communication, exosomes transfer specific cargos into HSCs from macrophages. Here, we show that exosomes derived from lipopolysaccharide (LPS)-treated macrophages has higher expression level of miR-500. And overexpression or inhibition of miR-500 in macrophage exosomes could promote or suppress HSC proliferation and activation. Treatment of exosomes with miR-500 overexpression can accelerate liver fibrosis in CCl4-induced liver fibrosis mouse model. miR-500 promotes HSC activation and liver fibrosis via suppressing MFN2. Moreover, miR-500 in serum exosomes could be a biomarker for liver fibrosis. Taken together, exosomal miR-500 derived from LPS-activated macrophages promotes HSC proliferation and activation by targeting MFN2 in liver fibrosis.

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Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

Regulatory Peptides ◽

10.1016/j.regpep.2007.08.014 ◽

2008 ◽

Vol 146 (1-3) ◽

pp. 73-79 ◽

Cited By ~ 45

Author(s):

Sevgin Özlem İşeri ◽

Göksel Şener ◽

Beyhan Saglam ◽

Feriha Ercan ◽

Nursal Gedik ◽

...

Keyword(s):

Biliary Obstruction ◽

Hepatic Injury ◽

Chronic Hepatic Injury

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Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests

Clinical Chemistry ◽

10.1093/clinchem/46.12.2027 ◽

2000 ◽

Vol 46 (12) ◽

pp. 2027-2049 ◽

Cited By ~ 268

Author(s):

D Robert Dufour ◽

John A Lott ◽

Frederick S Nolte ◽

David R Gretch ◽

Raymond S Koff ◽

...

Keyword(s):

Alanine Aminotransferase ◽

Laboratory Tests ◽

Hepatic Injury ◽

Total Error ◽

Performance Characteristics ◽

Published Data ◽

Medline Search ◽

Reference Limit ◽

Reference Limits ◽

Chronic Hepatic Injury

Abstract Purpose: To review information on performance characteristics for tests that are commonly used to identify acute and chronic hepatic injury. Data Sources and Study Selection: A MEDLINE search was performed for key words related to hepatic tests, including quality specifications, aminotransferases, alkaline phosphatase, γ-glutamyltransferase, bilirubin, albumin, ammonia, and viral markers. Abstracts were reviewed, and articles discussing performance of laboratory tests were selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. The drafts were also reviewed by the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and approved by the committee and the Association’s Council. Recommendations: Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, γ-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.

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Hepatocyte-Specific Ablation of PP2A Catalytic SubunitαAttenuates Liver Fibrosis Progression via TGF-β1/Smad Signaling

BioMed Research International ◽

10.1155/2015/794862 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Na Lu ◽

Yun Liu ◽

An Tang ◽

Lulu Chen ◽

Dengshun Miao ◽

...

Keyword(s):

Liver Fibrosis ◽

Knockout Mice ◽

Hepatic Injury ◽

Smooth Muscle Actin ◽

Hepatocyte Proliferation ◽

Mice Model ◽

Smad Signaling ◽

Physiological Processes ◽

Smad Phosphorylation ◽

Chronic Hepatic Injury

Protein phosphatase 2A (PP2A), a family of the major serine/threonine phosphatases in cells, regulates many aspects of physiological processes. However, isoform-specific substrates and the biological role of each specific member of the PP2A family remain largely unknown. In this study, we investigated whether PP2A catalytic subunit Cα(PP2Acα) is involved in chronic hepatic injury and fibrosis. A hepatocyte-specific PP2Acαablation mice model was established to examine the effect of PP2Acαon carbon tetrachloride- (CCl4-) induced chronic hepatic injury and fibrosis. Our results showed that PP2Acαknockout mice were less susceptible to chronic CCl4-induced liver injury as evidenced by lower levels of serum alanine aminotransferase and aspartate aminotransferase, decreased hepatocyte proliferation, and increased rate of apoptotic removal of the injured hepatocytes. PP2Acαknockout mice also displayed a lesser extent of liver fibrosis as a significant decrease in the proportion ofα-smooth muscle actin-expressing cells and collagen deposition was observed in their liver tissues. Furthermore, the levels of serum TGF-β1 and hepatocytic Smad phosphorylation were reduced in the PP2Acαknockout mice. These data suggest that hepatocyte-specific ablation of PP2Acαprotects against CCl4-induced chronic hepatic injury and fibrogenesis and the protective effect is mediated at least partially through the impaired TGF-β1/Smad signaling.

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