Hepatic stellate cells

Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C, Mukaida N. Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages and neovascularization. Int J Cancer 2006 118 335-345. 

Chor SY, Hui AY, To KF, et al. Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell. J Ethnopharmacol 2005 100 180-186. 

Kristensen DB et al. Proteome analysis of rat hepatic stellate cells. Hepatology 2000 32 266-277. 

Park, E.-J., Zhao, Y.-Z., Kim, J., and Sohn, D. H. (2006). A ginsenoside metabolite 20-O-P-D-glucopyranosyl-20(S)-protopanaxadiol, triggers apoptosis in activated rat hepatic stellate cells via caspase-3 activation. Planta Med. 11,1250-1253. 

Abbreviations AFP, a-fetoprotein CK, cytokeratin ECM, extracellular matrix EMT, epithelial to mesenchymal transition HCC, hepatocellular carcinoma HNF, hepatocyte nuclear factor, HSC, hepatic stellate cell MFB, myofibroblast M2-PK, M2-pyruvate kinase PDGF, platelet-derived growth factor TGF, transforming growth factor. 

Mikula M, Proell V, Fischer AN, Mikulits W (2006). Activated hepatic stellate cells induce tumor progression of neoplastic hepatocytes in a TGF-beta dependent fashion. J Cell Physiol 209 560-567. 

Proell V, Mikula M, Fuchs E, MIMIts W (2005). The plasticity of pl9 ARF null hepatic stellate cells and the dynamics of activation. Biochim Biophys Acta 1744 76-87. 

Figure 4.1. Schematic representation of the architecture of the liver. Blood enters the liver through the portal vein (PV) and hepatic arteries (HA), flows through the sinusoids, and leaves the liver again via the central vein (CV). KC, Kupffer cells SEC, sinusoidal endothelial cells HSC, hepatic stellate cells BD, bile duct. Modified from reference 98.

Figure 4.2. Diagram outlining the pathogenesis of liver fibrosis. Injury to parenchymal cells (PC) results in the activation of Kupffer cells (KC) and sinusoidal endothelial cells (SEC) and the recruitment of inflammatory cells (IC). These cells release cytokines, growth factors and reactive oxygen species that induce activation and proliferation of hepatic stellate cells (HSC). HSCs gradually transform into myofibroblasts (MF), the major producers of extracellular matrix (ECM) proteins.

When the receptor binding domain is encoded in a small peptide sequence, the peptide hg-and can also be synthesized and conjugated chemically to the carrier protein. This approach was followed in our laboratory by Beljaars et al. for the development of carriers aimed at the hepatic stellate cell, a cell type involved in liver fibrosis [33] (see also Chapter 4). A peptide sequence derived from the receptor binding domains of collagen VI was incorporated into a cyclic peptide homing device, and subsequently conjugated to lysine residues of HSA. This carrier bound selectively to activated hepatic stellate cells and rapidly accumulated in the livers of fibrotic rats. 

Phenolic and antioxidant substances have usually studied in red wines, however, recently, interest has increased in the study of bioactive phenolics in white wines Frega et al. [374] isolated and measured concentration of ethyl caffeoate in Verdicchio white wine by HPLC-tandem-mass spectrometry (HPLC-ESI-MS/MS) and they also determined its effects on hepatic stellate cells and intracellular peroxidation. The resnlts were interesting in the light of other studies demonstrating the relationship between reactive oxygen species, chronic liver injury, and hepatic fibrosis. 

Fu Y, Chen A. 2006. The phyto-chemical (—)-epigallocatechin gallate suppresses gene expression of epidermal growth factor receptor in rat hepatic stellate cells in vitro by reducing the activity of Egr-1. Biochem Pharmacol 72 227-238. 

Sakata R, Ueno T, Nakamura T, Sakamoto M, Torimura T, Sata M. 2004. Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth factor-induced proliferation of human hepatic stellate cell line LI90. J Hepatol 40 52-59. 

Williams EJ, Benyon RC, Trim N, Hadwin R, Grove BH, Arthur MJP, Unemori EN, Iredale JP. Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo. Gut 2001, 49, 577-583. 

Figure 1 Schematic representation of the architecture of the liver. Endothelial cells (EC) and Kupffer cells (KC) are located in close contact with the bloodstream, whereas hepatic stellate cells (HSC) and parenchymal cells (PC) reside in or behind the space of Disse.

Hepatocytes Kupffer cells Endothelial cells Hepatic stellate cells... 

Hepatic stellate cell activation is also associated with the induction of other liver diseases. In livers of patients with chronic hepatitis, an increased number of activated HSC were detected [87], Recently, an interaction of hepatitis C virus (HCV) with HSC was reported [88], Furthermore, HSC activation is associated with the development of liver tumors, for instance, hepatocellular carcinomas (HCC). Mediators like TGF-a and TGF-P derived from dysplastic hepatocytes... 

At present, attenuation of the hepatic stellate cell activities is an important goal of antifibrotic therapies, because this cell type is the major contributor to... 

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