Hepatic macrophages in liver fibrosis: pathogenesis and potential therapeutic targets

Li, Hai; You, Hong; Xu, Fan; Jia, Jidong

doi:10.1136/bmjgast-2016-000079

Cited by 62 publications

(61 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As liver macrophages have important functions in liver fibrosis and are abundant in the liver, they have been seen as a potential target for treating liver fibrosis [70]. Potential strategies targeting macrophages include preventing the infiltration of monocytes, antagonizing the pro-inflammatory cytokines they secrete, modifying the functional activation status of macrophages to promote the liver fibrinolysis [71][72][73].…”

Section: Macrophages In Liver Fibrosismentioning

confidence: 99%

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the second leading cause of cancer-related death worldwide. Fibrosis and cirrhosis are important risk factors for the development of HCC. Hepatic myofibroblasts are the cells responsible for extracellular matrix deposition, which is the hallmark of liver fibrosis. It is believed that myofibroblasts are predominantly derived from hepatic stellate cells (HSCs), also known as Ito cells. Nevertheless, depending on the nature of insult to the liver, it is thought that myofibroblasts may also originate from a variety of other cell types such as the portal fibroblasts (PFs), fibrocytes, hepatocytes, hepatic progenitor cells (HPCs), and mesothelial cells. Liver myofibroblasts are believed to transform into cancer-associated fibroblasts (CAFs) while HCC is developing. There is substantial evidence suggesting that activated HSCs (aHSCs)/cancer-associated fibroblasts (CAFs) may play an important role in HCC initiation and progression. In this paper, we aim to review current literature on cellular origins of myofibroblasts with a focus on hepatitis B virus (HBV)-and hepatitis C virus (HCV)-induced hepatic fibrosis. We also address the role of aHSCs/CAFs in HCC progression through the regulation of immune cells as well as mechanisms of evolvement of drug resistance.

show abstract

Section: Macrophages In Liver Fibrosismentioning

confidence: 99%

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Neutrophils secrete reactive oxygen species, ROS (7), while infiltrating monocytes differentiate into proinflammatory (M1) macrophages, which secrete additional inflammatory mediators (8). In the presence of inflammatory mediators, hepatic stellate cells lose their morphological characteristics and, within a few days from the initial injury event, become proliferative cells that produce large amounts of collagen-rich extracellular matrix (ECM), which accumulate in the space of Disse (9) and hinder molecule exchange between the blood and the parenchyma. These cells, also known as myofibroblasts, also contribute to the generation of ROS, which causes further damage in hepatocytes and endothelial cells, and TGF-β, which contributes to modulation of the macrophage phenotype (see text for details).…”

Section: Hypothesis: Activated Hscs Resemble Mesenchymal Stromal Cellmentioning

confidence: 99%

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Meirelles

Marson

Solari³

et al. 2020

Cells

View full text Add to dashboard Cite

Cirrhosis, a late form of liver disease, is characterized by extensive scarring due to exacerbated secretion of extracellular matrix proteins by myofibroblasts that develop during this process. These myofibroblasts arise mainly from hepatic stellate cells (HSCs), liver-specific pericytes that become activated at the onset of liver injury. Consequently, HSCs tend to be viewed mainly as myofibroblast precursors in a fibrotic process driven by inflammation. Here, the molecular interactions between liver pericytes and inflammatory cells such as macrophages and neutrophils at the first moments after injury and during the healing process are brought into focus. Data on HSCs and pericytes from other tissues indicate that these cells are able to sense pathogen- and damage-associated molecular patterns and have an important proinflammatory role in the initial stages of liver injury. On the other hand, further data suggest that as the healing process evolves, activated HSCs play a role in skewing the initial proinflammatory (M1) macrophage polarization by contributing to the emergence of alternatively activated, pro-regenerative (M2-like) macrophages. Finally, data suggesting that some HSCs activated during liver injury could behave as hepatic progenitor or stem cells will be discussed.

show abstract

“…By definition, NASH is an inflammatory disease, and numerous studies have implicated tissue‐resident hepatic macrophages (Kupffer cells [KCs]) in its pathogenesis and progression . Hepatic macrophages respond to diverse environmental signals and play central roles in the pathogenesis of acute and chronic liver injury, including inflammation, homeostasis, fibrosis, and resolution . Macrophages have been known to respond to lipid insults by producing proinflammatory mediators which putatively drive NAFLD .…”

mentioning

confidence: 99%

Dietary Lipids Differentially Shape Nonalcoholic Steatohepatitis Progression and the Transcriptome of Kupffer Cells and Infiltrating Macrophages

et al. 2019

View full text Add to dashboard Cite

A crucial component of nonalcoholic fatty liver disease (NAFLD) pathogenesis is lipid stress, which may contribute to hepatic inflammation and activation of innate immunity in the liver. However, little is known regarding how dietary lipids, including fat and cholesterol, may facilitate innate immune activation in vivo. We hypothesized that dietary fat and cholesterol drive NAFLD progression to steatohepatitis and hepatic fibrosis by altering the transcription and phenotype of hepatic macrophages. This hypothesis was tested by using RNA‐sequencing methods to characterize and analyze sort‐purified hepatic macrophage populations that were isolated from mice fed diets with varying amounts of fat and cholesterol. The addition of cholesterol to a high‐fat diet triggered hepatic pathology reminiscent of advanced nonalcoholic steatohepatitis (NASH) in humans characterized by signs of cholesterol dysregulation, generation of oxidized low‐density lipoprotein, increased recruitment of hepatic macrophages, and significant fibrosis. RNA‐sequencing analyses of hepatic macrophages in this model revealed that dietary cholesterol induced a tissue repair and regeneration phenotype in Kupffer cells (KCs) and recruited infiltrating macrophages to a greater degree than fat. Furthermore, comparison of diseased KCs and infiltrating macrophages revealed that these two macrophage subsets are transcriptionally diverse. Finally, direct stimulation of murine and human macrophages with oxidized low‐density lipoprotein recapitulated some of the transcriptional changes observed in the RNA‐sequencing study. These findings indicate that fat and cholesterol synergize to alter macrophage phenotype, and they also challenge the dogma that KCs are purely proinflammatory in NASH. Conclusion: This comprehensive view of macrophage populations in NASH indicates mechanisms by which cholesterol contributes to NASH progression and identifies potential therapeutic targets for this common disease.

show abstract

Hepatic macrophages in liver fibrosis: pathogenesis and potential therapeutic targets

Cited by 62 publications

References 50 publications

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Dietary Lipids Differentially Shape Nonalcoholic Steatohepatitis Progression and the Transcriptome of Kupffer Cells and Infiltrating Macrophages

Contact Info

Product

Resources

About