Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation

Blaya, Delia; Coll, Mar; Rodrigo-Torres, Daniel; Vila-Casadesús, María; Altamirano, José; Llopis, Marta; Graupera, Isabel; Perea, Luís; Aguilar-Bravo, Beatriz; Díaz, Alba; Bañales, Jesús M.; Clària, Joan; Lozano, Juan José; Bataller, Ramón; Caballería, Juan; Ginès, Pere; Sancho‐Bru, Pau

doi:10.1136/gutjnl-2015-311314

Cited by 101 publications

(86 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a study that reported a histological scoring system to determine severity of AH, presence of cholestasis was found to be an independent predictor of increased mortality . In another study, the microRNA profile of AH patients was analyzed and found to reflect changes observed in cholestatic liver diseases . These findings collectively suggest that cholestasis is a frequent complication of AH and may even portend a worse outcome.…”

Section: Discussionmentioning

confidence: 97%

Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes

et al. 2018

View full text Add to dashboard Cite

Clinical conditions that result in endotoxemia, such as sepsis and alcoholic hepatitis, often are accompanied by cholestasis. Although hepatocellular changes in response to lipopolysaccharide (LPS) have been well characterized, less is known about whether and how cholangiocytes contribute to this form of cholestasis. We examined effects of endotoxin on expression and function of the type 3 inositol trisphosphate receptor (ITPR3), because this is the main intracellular Ca release channel in cholangiocytes, and loss of it impairs ductular bicarbonate secretion. Bile duct cells expressed the LPS receptor TLR4, which links to activation of NF-κB. Analysis of the human ITPR3 promoter revealed five putative response elements to NF-κB, and promoter activity was inhibited by p65/p50. Nested 0.5 and 1.0 kb deletion fragments of the ITPR3 promoter were inhibited by NF-κB subunits. ChIP assay showed that NF-κB interacts with the ITPR3 promoter, with an associated increase in H3K9 methylation. LPS decreased ITPR3 mRNA and protein expression, and also decreased sensitivity of bile duct cells to calcium agonist stimuli. This reduction was reversed by inhibition of TLR4. ITPR3 expression was decreased or absent in cholangiocytes from patients with cholestasis of sepsis and from patients with severe alcoholic hepatitis CONCLUSION: Stimulation of TLR4 via LPS activates NF-κB to downregulate ITPR3 expression in human cholangiocytes. This may contribute to the cholestasis that can be observed in conditions such as sepsis or alcoholic hepatitis. This article is protected by copyright. All rights reserved.

show abstract

Section: Discussionmentioning

confidence: 97%

Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes

et al. 2018

View full text Add to dashboard Cite

show abstract

“…21, 33 It has been reported that overexpression of miR-182 induces the production of inflammatory mediators in biliary cells and increase liver damage, bile acid accumulation, and inflammatory responses in mice. 34 However, the role of miR-182 in atherogenesis remained unclear. In the present study, we found that miR-182 promoted LPL expression, lipid accumulation, and proinflammatory cytokine secretion by targeting HDAC9 in THP-1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice

Cheng

Gong

Zhao

et al. 2017

Circ J

View full text Add to dashboard Cite

“…More recently, Blaya D et al also identified 177 differentially expressed miRNAs in the liver of ALD patients (Blaya et al, 2016). In their studies, RNA samples from liver tissue of patients with severe AH, alcoholic cirrhosis, cirrhosis from hepatitis C, and healthy patients were examined and compared.…”

Section: The Role Of Microrna In Inflammation Of Aldmentioning

confidence: 99%

“…MiR-182 mimic induced an upregulation of inflammatory mediators in biliary cells, suggest that miR-182 promotes liver inflammation by targeting biliary epithelial cells (Blaya et al, 2016). …”

Section: The Role Of Microrna In Inflammation Of Aldmentioning

confidence: 99%

Targeting inflammation for the treatment of alcoholic liver disease

Zhou

Parker

et al. 2017

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) is a leading cause of chronic liver disease with a wide spectrum of manifestations including simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Liver injury in ALD is caused by chronic inflammation, which has been actively investigated as a therapeutic target for the treatment of ALD for over the last four decades. In this review, we summarize a wide variety of inflammatory mediators that have been shown to contribute to the pathogenesis of ALD, and discuss the therapeutic potential of these mediators for the treatment of ALD.

show abstract

Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation

Abstract: AH is characterised by a deregulated miRNA profile, including miR-182, which is associated with disease severity and liver injury. These results highlight the potential of miRNAs as therapeutic targets and biomarkers in AH.

Cited by 101 publications

References 50 publications

Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes

Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice

Targeting inflammation for the treatment of alcoholic liver disease

Contact Info

Product

Resources

About