2011
DOI: 10.1152/ajpgi.00451.2010
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Therapeutic targets in liver fibrosis

Abstract: Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licens… Show more

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Cited by 115 publications
(91 citation statements)
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“…Lipophilic ligand conjugations can enhance delivery to NP cells. NP cells consist of sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, which express disease-related genes causing inflammation (Huang et al, 2013) and fibrosis (Fallowfield, 2011). Although our findings represent an important step in advancing ligand selection tailored to the expression cells of disease-related genes, additional studies are required to isolate the sinusoidal endothelial cells and Kupffer cells as described previously (Bijsterbosch et al, 2000) and evaluate the efficacy.…”
Section: Discussionmentioning
confidence: 85%
See 1 more Smart Citation
“…Lipophilic ligand conjugations can enhance delivery to NP cells. NP cells consist of sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, which express disease-related genes causing inflammation (Huang et al, 2013) and fibrosis (Fallowfield, 2011). Although our findings represent an important step in advancing ligand selection tailored to the expression cells of disease-related genes, additional studies are required to isolate the sinusoidal endothelial cells and Kupffer cells as described previously (Bijsterbosch et al, 2000) and evaluate the efficacy.…”
Section: Discussionmentioning
confidence: 85%
“…Disease-related genes causing hyperlipidemia and diabetes are expressed in hepatocytes, which account for a large proportion (approximately 80%) of liver volume (Sehgal et al, 2013). On the other hand, NP cells account for only a small proportion of liver volume and consist of several cell types, such as sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, that express disease-related genes causing inflammation (Huang et al, 2013) and fibrosis (Fallowfield, 2011). Several studies have been conducted to aid the development of drug delivery systems to the liver using ligand conjugation.…”
Section: Introductionmentioning
confidence: 99%
“…During fi brosis progression, the main ECM-producing cells are activated HSCs, which secrete ECM proteins including collagen I and III (17). Cross-remodeling of the ECM in the fibrotic liver is likely to be regulated by the synthesis and enzymatic degradation of the ECM.…”
Section: Discussionmentioning
confidence: 99%
“…There are 3 major pathways that may help eliminate the activated HSCs: apoptosis, senescence, or reversal to an inactivated phenotype. In recent years, induction of apoptosis to eliminate HSCs has been suggested to be effective in the control of hepatic fibrosis (Fallowfield 2011;Tacke and Weiskirchen 2012). Diallyl trisulfide (DATS; 3-(prop-2-enyltrisulfanyl)prop-1-ene, CH 2 =CHCH 2 -SSS-CH 2 CH=CH 2 , molecular weight 178.33), a characteristic flavor produced by garlic, contains 3 sulfur atoms with 2 allyl groups.…”
Section: Introductionmentioning
confidence: 99%