Stellate cell

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. 

The most abundant cell type in the liver is the hepatocyte, other cells in the liver are the non-parenchymal cells Kupffer cells, the resident macrophages of the liver, endothelial cells and stellate cells. These cells have been discussed in more detail in Chapter 4. 

Isolation from human liver of other cell types, such as Kupffer, endothelial and stellate cells has also been developed and extensively reviewed [29-31]. 

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. 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Retinyl esters and the P-carotene are incorporated into chylomicrons and taken up mainly by hepatocytes. In the liver retinol may be stored in stellate cells as retinyl esters, oxidized to retinoic acid or liberated into cells bound to retinol-binding proteins (RBP). All E retinoic acid and its 9Z isomer have an affinity for nuclear receptors. They activate the transcription and bind as dimers to specific nucleotide sequences, present in promoters of target genes. 

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. 

Gospodarowicz D, Abraham JA, Schilling J. 1989. Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci USA. 86 7311-7315. 

Chapman, L.P., Epton, M.J., Buckingham, J.C., Morris, J.F., and H.C. Christian, 2003, Evidence for a role of the adenosine S -triphosphate-binding cassette transporter A1 in the externalization of annexin I from pituitary folliculo-stellate cells. Endocrinology.l44(3) 1062—73. 

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. 

Pertwee RG, Fernando SR (1996) Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder. Br J Pharmacol 118(8) 2053—8 Pitler TA, Alger BE (1992) Postsynaptic spike firing reduces synaptic GABAa responses in hippocampal pyramidal cells. J Neurosci 12 4122-32 Porter AC, Sauer JM, Knierman MD, Becker GW, Bema MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC (2002) Characterization of a novel endocannabinoid, vi-rodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301(3) 1020-4 Rancillac A, Barbara JG (2005) Frequency-dependent recruitment of inhibition mediated by stellate cells in the rat cerebellar cortex. J Neurosci Res 80(3) 414-23... 

Soler-Llavina GJ, Sabatini BL (2006) Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9(6) 798-806 Stanton PK, Bramham C, Scharfman H (eds) (2005) Synaptic plasticity and transsynaptic signaling. Spinger, New York pp. 457-68... 

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