Advances in cholangiocyte immunobiology

Syal, Gaurav; Fausther, Michel; Dranoff, Jonathan A.

doi:10.1152/ajpgi.00227.2012

Cited by 83 publications

(77 citation statements)

References 105 publications

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“…Treatment with CCl 4 is hepatotoxic, causing necrosis of hepatocytes and inflammation in the pericentrolobular area. However, BDL induces obstruction of bile flow with increased biliary pressure, moderate inflammation, and cytokine secretion by biliary epithelial cells (64). Diffusion (accumulation) of free bile acids may trigger ductular reaction (hyperplastic response of bile duct epithelial cells), resulting in activation of cholangiocytes and portal fibroblasts.…”

Section: Ahscs and Apfs Contribute Differently To Liver Fibrosis Of Dmentioning

confidence: 99%

“…Furthermore, our in vitro conditions may not mimic the complex liver microenvironment required for bile acid stimulation of PFs (17). Alternatively, bile acids may indirectly induce PF activation by affecting cholangiocytes (68) or hepatocytes (65) that, in turn, may facilitate selective aPF activation via cell-cell signaling or cytokine secretion (64). In addition, specific factors produced by activated cholangiocytes may presensitize PFs for bile acid stimulation (69).…”

Section: Ahscs and Apfs Contribute Differently To Liver Fibrosis Of Dmentioning

confidence: 99%

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Origin of myofibroblasts in the fibrotic liver in mice

Iwaisako

Jiang

Zhang³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

454

461

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Significance Liver resident activated hepatic stellate cells (aHSCs), and activated portal fibroblasts (aPFs) are the major source of the fibrous scar in the liver. aPFs have been implicated in liver fibrosis caused by cholestatic liver injury, whereas fibrosis in hepatotoxic liver injury is attributed to aHSCs. However, the contribution of aPFs to cholestatic fibrosis is not well characterized because of difficulties in cell purification and the lack of identified aPF-specific markers. We have developed a novel flow cytometry-based method of aPFs purification from the nonparenchymal cell fraction of collagen-α1(I)-GFP mice and have identified potential aPF-specific markers. The goal of this study is to determine whether aPFs contribute to cholestatic liver fibrosis and identify the mechanism(s) of their activation.

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Section: Ahscs and Apfs Contribute Differently To Liver Fibrosis Of Dmentioning

confidence: 99%

Section: Ahscs and Apfs Contribute Differently To Liver Fibrosis Of Dmentioning

confidence: 99%

Origin of myofibroblasts in the fibrotic liver in mice

Iwaisako

Jiang

Zhang³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

454

461

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“…Here changes are confined to the periportal area, with a mixed inflammatory cell infiltrate leading to periportal fibrosis. Interestingly, inflammation and fibrosis are not necessarily closely associated because the risk of biliary dysplasia and malignancy is not correlated with disease duration or severity (47,327). Additionally, primary sclerosing cholangitis can lead to sinusoidal hypertension before development of varices and hemorrhages associated with cirrhosis (335).…”

Section: G818 Dynamics Of the Extracellular Matrix In Liver Fibrosismentioning

confidence: 99%

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Karsdal

Manon‐Jensen

Genovese

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

223

176

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Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases.collagen; cytokine; extracellular fibrogenesis; integrin; laminin; matrix metalloproteinase; posttranslational modification; proteoglycan; endocrine 45% OF ALL DEATHS IN THE DEVELOPED WORLD are associated with chronic fibroproliferative diseases (256, 378). Thus there is an increasing need to address fibroproliferative diseases because of their strong impact on the quality of life and health costs consequent to pain and organ failure, with an increased need for organ transplants despite dwindling availability, often followed by death. Moreover, their severity and perceived irreversibility in view of a current paucity of treatment options, coupled with a high prevalence in most and an orphan status in some fibrotic diseases, have just begun to attract biotechnology and big pharmaceutical companies to the field.The common denominator of fibroproliferative diseases is a dysregulated tissue remodeling leading to the excessive and abnormal accumulation of extracellular matrix (ECM) components, thereby generating an ECM with different structural and signaling properties in the affected tissues (285, 287, 289, 378 -380). Fibrosis can affect almost any organ or tissue and is therefore associated with a wide variety of diseases and injuries (287). Figure 1 illustrates the major fibroproliferative diseases with a significant impact on human health (20, ...

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“…Immunological factors (e.g., ABO blood type incompatibility [37,38] and cytomegalovirus infection [39]) are also associated with non-BAS formation. Because cholangiocytes play an important role in mucosal immunity in the biliary system [40,41], they are the primary targets of immune attack, which leads to stricture formation.…”

Section: Etiologies and Risk Factors For Biliary Strictures After Ldltmentioning

confidence: 99%

Endoscopic management of biliary strictures after living donor liver transplantation

Tsujino

Isayama

Kogure

et al. 2017

Clin J Gastroenterol

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Living donor liver transplantation (LDLT) is an effective alternative to deceased liver transplantation (DDLT) for end-stage liver disease. Although advances in surgical techniques, immunosuppressive management, and post-transplant care have improved the overall outcomes of LDLT, biliary strictures remain the major unsolved problem. Endoscopic retrograde cholangiopancreatography (ERCP) is currently considered the first-line therapy for biliary strictures following LDLT with duct-to-duct reconstruction, with percutaneous and surgical interventions reserved for patients with unsuccessful management via ERCP. Endoscopic management of biliary strictures is technically more challenging in LDLT than in DDLT because of the complexity of the biliary anastomosis, in addition to the tortuous and angulated biliary system. Placement of one or more plastic stents after balloon dilation has been the standard strategy for post-LDLT stricture, but this requires multiple stent exchange to prevent stent occlusion until stricture resolution. Inside stents might prevent duodenobiliary reflux and thus have longer stent patency, obviating the need for multiple ERCPs. Newly developed covered self-expandable metallic stents with anti-migration systems are alternatives to the placement of multiple plastic stents. With the advent of deep enteroscopy, biliary strictures in LDLT patients with Rouxen-Y hepaticojejunostomy are now treatable endoscopically. In this review, we discuss the short-and long-term outcomes of endoscopic management of post-LDLT strictures as well as recent advances in this field.

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Advances in cholangiocyte immunobiology

Cited by 83 publications

References 105 publications

Origin of myofibroblasts in the fibrotic liver in mice

Origin of myofibroblasts in the fibrotic liver in mice

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Endoscopic management of biliary strictures after living donor liver transplantation

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