Mast Cells Regulate Ductular Reaction and Intestinal Inflammation in Cholestasis Through Farnesoid X Receptor Signaling

Meadows, Vik; Kennedy, Lindsey; Ekser, Burçin; Kyritsi, Konstantina; Kundu, Debjyoti; Zhou, Tianhao; Chen, Lixian; Pham, Linh; Wu, Nan; Demieville, Jennifer; Hargrove, Laura; Glaser, Shannon; Alpini, Gianfranco; Francis, Heather

doi:10.1002/hep.32028

Cited by 43 publications

(31 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aside from cholangiocytes, mast cells secrete TGF-β1 and induce biliary senescence and other markers of cholestasis (Kyritsi et al, 2021), which is an important feature considering that mast cell migration to portal areas is a key feature and damaging component of cholestasis (Wilcox et al, 1986;Tsuneyama et al, 1999;Jones et al, 2016). Mast cell farnesoid X receptor (FXR) signaling promotes biliary senescence and associated biliary and liver damage in murine models of PSC (Meadows et al, 2021). Mast cell-derived components lend to worsening phenotypes in PSC and understanding if they can be targeted to mediate damage is a topic of research currently.…”

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Meadows

Baiocchi

Kundu

et al. 2021

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

Cellular senescence is a pathophysiological phenomenon in which proliferative cells enter cell cycle arrest following DNA damage and other stress signals. Natural, permanent DNA damage can occur after repetitive cell division; however, acute stress or other injuries can push cells into premature senescence and eventually a senescence-associated secretory phenotype (SASP). In recent years, there has been increased evidence for the role of premature senescence in disease progression including diabetes, cardiac diseases, and end-stage liver diseases including cholestasis. Liver size and function change with aging, and presumably with increasing cellular senescence, so it is important to understand the mechanisms by which cellular senescence affects the functional nature of the liver in health and disease. As well, cells in a SASP state secrete a multitude of inflammatory and pro-fibrogenic factors that modulate the microenvironment. Cellular SASP and the associated, secreted factors have been implicated in the progression of liver diseases, such as cholestatic injury that target the biliary epithelial cells (i.e., cholangiocytes) lining the bile ducts. Indeed, cholangiocyte senescence/SASP is proposed to be a driver of disease phenotypes in a variety of liver injuries. Within this review, we will discuss the impact of cholangiocyte senescence and SASP in the pathogenesis of cholestatic disorders.

show abstract

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Meadows

Baiocchi

Kundu

et al. 2021

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…NEFA and total bile acids (TBA) [ 25 , 26 ] are also closely related to microbial and metabolic disorders. Elevated levels of TBA are also associated with cholestasis and hepatic lipid metabolism disorders [ 27 , 28 ]. The Model group showed high levels of NEFA and TBA, significantly different from the standard diet STD group ( p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota

et al. 2022

View full text Add to dashboard Cite

(1) Background: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders. (2) Methods: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation. (3) Conclusions: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.

show abstract

“…75 MCs release various cytokines that impact the intestinal barrier directly and also express FXR in the intestine and liver, which alters intestinal fibroblast growth factor 15 and promotes liver fibrosis. 76 Immunoglobulin A (IgA) secreted by lymphocytes and plasma cells have a key role in barrier immune function. Secretory IgA is the major subtype in the gut to protect the intestinal epithelium from pathogenic micro-organisms and maintain the homeostasis in regulation of microbiota composition.…”

Section: Role Of the Intestinal Immunological Barrier In Nafld Develo...mentioning

confidence: 99%

Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Liu¹,

Yin²,

Gao³

et al. 2022

J Clin Transl Hepatol

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The mechanisms involved in NAFLD onset are complicated and multifactorial. Recent literature has indicated that altered intestinal barrier function is related to the occurrence and progression of liver disease. The intestinal barrier is important for absorbing nutrients and electrolytes and for defending against toxins and antigens in the enteric environment. Major mechanisms by which the intestinal barrier influences the development of NAFLD involve the altered epithelial layer, decreased intracellular junction integrity, and increased intestinal barrier permeability. Increased intestinal permeability leads to luminal dysbiosis and allows the translocation of pathogenic bacteria and metabolites into the liver, inducing inflammation, immune response, and hepatocyte injury in NAFLD. Although research has been directed to NAFLD in recent decades, the pathophysiological changes in NAFLD initiation and progression are still not completely understood, and the therapeutic targets remain limited. A deeper understanding on the correlation between NAFLD pathogenesis and intestinal barrier regulation must be attained. Therefore, in this review, the components of the intestinal barrier and their respective functions and disruptions during the progression of NAFLD are discussed.

show abstract

Mast Cells Regulate Ductular Reaction and Intestinal Inflammation in Cholestasis Through Farnesoid X Receptor Signaling

Cited by 43 publications

References 46 publications

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota

Intestinal Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Contact Info

Product

Resources

About