NOX1/nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase promotes proliferation of stellate cells and aggravates liver fibrosis induced by bile duct ligation

Hepatology ◽  
2011 ◽  
Vol 54 (3) ◽  
pp. 949-958 ◽  
Author(s):  
Wenhao Cui ◽  
Kuniharu Matsuno ◽  
Kazumi Iwata ◽  
Masakazu Ibi ◽  
Misaki Matsumoto ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Bile Duct Ligation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Stellate Cells ◽  
Nicotinamide Adenine ◽  
Reduced Form ◽  
Duct Ligation

Functional coupling of FcγRI to nicotinamide adenine dinucleotide phosphate (reduced form) oxidative burst and immune complex trafficking requires the activation of phospholipase D1

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3421-3428 ◽  
Author(s):  
Alirio J. Melendez ◽  
Luce Bruetschy ◽  
R. Andres Floto ◽  
Margaret M. Harnett ◽  
Janet M. Allen
Keyword(s):  
Nadph Oxidase ◽  
Immune Complexes ◽  
Nicotinamide Adenine Dinucleotide ◽  
Intracellular Signaling ◽  
Antisense Oligonucleotides ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Sphingosine Kinase ◽  
Calcium Transients ◽  
Nicotinamide Adenine ◽  
Reduced Form

Abstract Immunoglobulin G (IgG) receptors (FcγRs) on myeloid cells are responsible for the internalization of immune complexes. Activation of the oxidase burst is an important component of the integrated cellular response mediated by Fc receptors. Previous work has demonstrated that, in interferon-γ–primed U937 cells, the high-affinity receptor for IgG, FcγRI, is coupled to a novel intracellular signaling pathway that involves the sequential activation of phospholipase D (PLD), sphingosine kinase, and calcium transients. Here, it is shown that both known PLD isozymes, PLD1 and PLD2, were present in these cells. With the use of antisense oligonucleotides to specifically reduce the expression of either isozyme, PLD1, but not PLD2, was found to be coupled to FcγRI activation and be required to mediate receptor activation of sphingosine kinase and calcium transients. In addition, coupling of FcγRI to activation of the nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase burst was inhibited by pretreating cells with 0.3% butan-1-ol, indicating an absolute requirement for PLD. Furthermore, use of antisense oligonucleotides to reduce expression of PLD1 or PLD2 demonstrated that PLD1 is required to couple FcγRI to the activation of NADPH oxidase and trafficking of internalized immune complexes for degradation. These studies demonstrate the critical role of PLD1 in the intracellular signaling cascades initiated by FcγRI and its functional role in coordinating the response to antigen-antibody complexes.

scholarly journals 3,5-Diethoxy-3′-Hydroxyresveratrol (DEHR) Ameliorates Liver Fibrosis via Caveolin-1 Activation in Hepatic Stellate Cells and in a Mouse Model of Bile Duct Ligation Injury

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2833 ◽  
Author(s):  
Phil Lee ◽  
Hye-Jin Park ◽  
Namki Cho ◽  
Hong Kim
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Western Blot ◽  
Hepatic Stellate Cells ◽  
Bile Duct Ligation ◽  
B Cell Lymphoma ◽  
Stellate Cells ◽  
Transfected Cells ◽  
Caveolin 1 ◽  
Duct Ligation

Hepatic stellate cells (HSCs) are involved in the pathogenesis of liver fibrosis. Resveratrol, 3,5,4′-trihydroxystilbene, is a dietary polyphenol found in natural food products. Here, we evaluated the anti-proliferative effects of a synthetic resveratrol derivative, 3,5-diethoxy-3′-hydroxyresveratrol (DEHR), on HSCs. Flow cytometry and Western blot analyses showed that DEHR induces apoptosis through the upregulation of cleaved caspase-3 and poly (ADP-ribose) polymerase expression and reduction in the level of an anti-apoptotic protein B-cell lymphoma 2 (Bcl2). As caveolin-1 (CAV1), a competitive inhibitor of heme oxygenase 1 (HO-1), is related to apoptotic proteins in hepatic cells, we focused on the role of CAV1 in DEHR-induced apoptosis in HSCs through Western blot analyses. Our results showed that the inhibitory effect of DEHR on cell viability was stronger in HO-1 siRNA-transfected cells but weakened in CAV1 siRNA-transfected cells. Collagen concentration was significantly reduced, whereas CAV1 expression increased after treatment of a bile duct ligation injury-induced liver fibrosis model with DEHR for four weeks. We confirmed that DEHR treatment significantly reduced fibrous hyperplasia around the central veins, using hematoxylin and eosin and Sirius red staining. DEHR ameliorates liver fibrosis in vitro and in vivo, possibly through a mechanism involving CAV1.

Adenoviral CCN3/NOV gene transfer fails to mitigate liver fibrosis in an experimental bile duct ligation model because of hepatocyte apoptosis

2012 ◽  
Vol 32 (9) ◽  
pp. 1342-1353 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Sebastian Huss ◽  
Eddy Leur ◽  
Ute Haas ◽  
Ralf Weiskirchen
Keyword(s):  
Bile Duct ◽  
Gene Transfer ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Hepatocyte Apoptosis ◽  
Duct Ligation

scholarly journals PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA

FEBS Letters ◽  
2007 ◽  
Vol 581 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Hongtao Wang ◽  
Yan Zhang ◽  
Robert O. Heuckeroth
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Pai 1

NADPH oxidase promotes NF-κB activation and proliferation in human airway smooth muscle

2002 ◽  
Vol 282 (4) ◽  
pp. L782-L795 ◽  
Author(s):  
Sukhdev S. Brar ◽  
Thomas P. Kennedy ◽  
Anne B. Sturrock ◽  
Thomas P. Huecksteadt ◽  
Mark T. Quinn ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Nadph Oxidase ◽  
Airway Smooth Muscle ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Nicotinamide Adenine ◽  
Phagocytic Cells ◽  
Diphenylene Iodonium ◽  
Reduced Nicotinamide Adenine Dinucleotide

Evidence is rapidly accumulating that low-activity-reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases homologous to that in phagocytic cells generate reactive oxygen species as signaling intermediates in both endothelium and vascular smooth muscle. We therefore explored the possibility of such an oxidase regulating growth of airway smooth muscle (AWSM). Proliferation of human AWSM cells in culture was inhibited by the antioxidants catalase and N-acetylcysteine, and by the flavoprotein inhibitor diphenylene iodonium (DPI). Membranes prepared from human AWSM cells generated superoxide anion (O[Formula: see text]) measured by superoxide dismutase-inhibitable lucigenin chemiluminescence, with a distinct preference for NADPH instead of reduced nicotinamide adenine dinucleotide as substrate. Chemiluminescence was also inhibited by DPI, suggesting the presence of a flavoprotein containing oxidase generating O[Formula: see text] as a signaling molecule for cell growth. Examination of human AWSM cells by reverse transcriptase-polymerase chain reaction consistently demonstrated transcripts with sequences identical to those reported for p22phox. Transfection with p22phoxantisense oligonucleotides reduced human AWSM proliferation. Inhibition of NADPH oxidase activity with DPI prevented serum-induced activation of nuclear factor-κB (NF-κB), and overexpression of a superrepressor form of the NF-κB inhibitor IκBα significantly reduced human AWSM growth. These findings suggest that an NADPH oxidase containing p22phoxregulates growth-factor responsive human AWSM proliferation, and that the oxidase signals in part through activation of the prototypical redox-regulated transcription factor NF-κB.

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