The soluble guanylate cyclase stimulator IW‐1973 prevents inflammation and fibrosis in experimental non‐alcoholic steatohepatitis

The soluble guanylate cyclase stimulator IW‐1973 prevents inflammation and fibrosis in... AbbreviationsATGautophagy‐related proteinBATbrown adipose tissueCDAAHcholine‐deficient, l‐amino acid‐defined, high‐fatCOL1A1/COL1A2collagen type I α1/α2FAT/CD36fatty acid translocaseGUCY1A2guanylate cyclase 1 soluble subunit α2HFDhigh‐fat dietHSLhormone‐sensitive lipaseIL‐1raIL‐1 receptor antagonistLC3microtubule‐associated proteins 1A/1B light chain 3MCP‐1monocyte chemotactic protein 1NAFLDnon‐alcoholic fatty liver diseaseNASnon‐alcoholic fatty liver disease activity scoreNASHnon‐alcoholic steatohepatitissGCsoluble GCSREBP‐1csterol response element‐binding protein 1cTAGstriglyceridesUCP1uncoupling protein 1VASPvasodilator‐stimulated phosphoproteinWATwhite adipose tissueα‐SMAα‐smooth muscle actinIntroductionNon‐alcoholic fatty liver disease (NAFLD) is a multifaceted condition that includes pathological manifestations ranging from the accumulation of neutral lipids in the cytoplasm of hepatocytes (steatosis) to the combination of steatosis with inflammation, a stage known as non‐alcoholic steatohepatitis (NASH) (Sanyal, ). NASH is the aggressive form of NAFLD and increases the risk for advanced liver disease culminating in hepatic fibrosis, cirrhosis and hepatocarcinoma (Sanyal, ). The mechanisms underlying the progression of NASH have not been completely elucidated, but repeated insults to the liver of these patients lead to inflammatory injury, hepatocyte death and the expansion of extracellular matrix (fibrosis) (Friedman, ). Therefore, pharmacological interventions that protect liver cells from inflammatory injury and fibrosis could be useful as a therapy for NASH.Cyclic nucleotides, such as cGMP, play a major role in cell signalling and tissue homeostasis. Pharmacological modulation of the cGMP pathway is a potential target for therapy in complex http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

The soluble guanylate cyclase stimulator IW‐1973 prevents inflammation and fibrosis in experimental non‐alcoholic steatohepatitis

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Publisher
Wiley
Copyright
© 2018 The British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1111/bph.14137
Publisher site
See Article on Publisher Site

Abstract

AbbreviationsATGautophagy‐related proteinBATbrown adipose tissueCDAAHcholine‐deficient, l‐amino acid‐defined, high‐fatCOL1A1/COL1A2collagen type I α1/α2FAT/CD36fatty acid translocaseGUCY1A2guanylate cyclase 1 soluble subunit α2HFDhigh‐fat dietHSLhormone‐sensitive lipaseIL‐1raIL‐1 receptor antagonistLC3microtubule‐associated proteins 1A/1B light chain 3MCP‐1monocyte chemotactic protein 1NAFLDnon‐alcoholic fatty liver diseaseNASnon‐alcoholic fatty liver disease activity scoreNASHnon‐alcoholic steatohepatitissGCsoluble GCSREBP‐1csterol response element‐binding protein 1cTAGstriglyceridesUCP1uncoupling protein 1VASPvasodilator‐stimulated phosphoproteinWATwhite adipose tissueα‐SMAα‐smooth muscle actinIntroductionNon‐alcoholic fatty liver disease (NAFLD) is a multifaceted condition that includes pathological manifestations ranging from the accumulation of neutral lipids in the cytoplasm of hepatocytes (steatosis) to the combination of steatosis with inflammation, a stage known as non‐alcoholic steatohepatitis (NASH) (Sanyal, ). NASH is the aggressive form of NAFLD and increases the risk for advanced liver disease culminating in hepatic fibrosis, cirrhosis and hepatocarcinoma (Sanyal, ). The mechanisms underlying the progression of NASH have not been completely elucidated, but repeated insults to the liver of these patients lead to inflammatory injury, hepatocyte death and the expansion of extracellular matrix (fibrosis) (Friedman, ). Therefore, pharmacological interventions that protect liver cells from inflammatory injury and fibrosis could be useful as a therapy for NASH.Cyclic nucleotides, such as cGMP, play a major role in cell signalling and tissue homeostasis. Pharmacological modulation of the cGMP pathway is a potential target for therapy in complex

Journal

British Journal of PharmacologyWiley

Published: Jan 1, 2018

References

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