Rat liver perisinusoidal lipocytes (PL) cultured on uncoated plastic transform spontaneously within 6-10 d to myofibroblastlike cells (MFBlC). Parallel to the transformation the TGF alpha- and TGF beta 1-mRNA expression increased and was highest in MFBlC. Competitive radioligand binding assays demonstrated that in contrast to untransformed PL the MFBlC synthesize and secrete transforming growth factor (TGF)-alpha (15 fmol/cell per 24 h) and predominantly the latent form of TGF beta 1 (0.2 fmol/cell per 24 h). Medium conditioned by MFBlC (MFBcM) significantly stimulated PL proliferation with little effect on PL proteoglycan synthesis. By transient acidification of the MFBcM, known to activate the latent form of TGF beta 1, the stimulatory effect on PL proteoglycan synthesis was enhanced and furthermore PL transformation (measured by expression of iso-alpha smooth muscle actin and loss of retinylpalmitate) was accelerated. Preincubation of this medium with neutralizing antibodies to TGF beta resulted in (a) the growth inhibitory effect was converted to a growth stimulation and (b) the stimulatory effect on proteoglycan synthesis was abolished. In summary our data indicate that progressive activation of PL on plastic (transformation to MFBlC) leads to an enhanced expression of the TGF alpha- and TGF beta 1-mRNAs and secretion of the corresponding proteins. Medium conditioned by MFBIC stimulates proliferation, transformation, and PG synthesis of untransformed PL. These mechanisms are suggested to be relevant in self perpetuation of liver fibrogenesis.
M G Bachem, D Meyer, R Melchior, K M Sell, A M Gressner
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Transcriptional Activation of Transforming Growth Factor β1 and Its Receptors by the Kruppel-like Factor Zf9/Core Promoter-binding Protein and Sp1: POTENTIAL MECHANISMS FOR AUTOCRINE FIBROGENESIS IN RESPONSE TO INJURY
Y Kim, V Ratziu, SG Choi, A Lalazar, G Theiss, Q Dang, SJ Kim, SL Friedman |
The Journal of biological chemistry | 1998 |
Expression of Interleukin-10 by in Vitro and in Vivo Activated Hepatic Stellate Cells
SC Wang, M Ohata, L Schrum, RA Rippe, H Tsukamoto |
The Journal of biological chemistry | 1998 |
Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis
MJ Arthur, DA Mann, JP Iredale |
Journal of Gastroenterology and Hepatology | 1998 |
Analysis of the expression pattern of the latent transforming growth factor ? binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge region
K Michel, S Roth, C Trautwein, WR Gong, P Flemming, AM Gressner |
Hepatology | 1998 |
Liver Growth and Repair
A Strain, AM Diehl |
1998 | |
Molecular mechanisms of hepatic fibrosis and principles of therapy
SL Friedman |
Journal of Gastroenterology | 1997 |
Tissue inhibitors of metalloproteinases in liver fibrosis
JP Iredale |
The International Journal of Biochemistry & Cell Biology | 1997 |
Myofibroblasts of Palmar Fibromatosis co-express transforming growth factor-alpha and epidermal growth factor receptor
G Magro, E Lanterni, G Micali, G Paravizzini, S Travali, S Lanzafame |
The Journal of Pathology | 1997 |
Functional analysis of the lysyl oxidase promoter in myofibroblast-like clones of 3T6 fibroblast
CJ Saux, C Gleyzal, M Raccurt, P Sommer |
Journal of Cellular Biochemistry | 1997 |
Effect of Acetaldehyde on Sp1 Binding and Activation of the Mouse α2(I) Collagen Promoter
K Miao, JJ Potter, FA Anania, L Rennie-Tankersley, E Mezey |
Archives of Biochemistry and Biophysics | 1997 |
Halofuginone, a specific inhibitor of collagen type I synthesis, prevents dimethylnitrosamine-induced liver cirrhosis
M Pines, V Knopov, O Genina, I Lavelin, A Nagler |
Journal of Hepatology | 1997 |
TGF-β-mediated hepatocellular apoptosis by rat and human hepatoma cells and primary rat hepatocytes
AM Gressner, B Lahme, HG Mannherz, B Polzar |
Journal of Hepatology | 1997 |
Transforming growth factor-β-induced collagen synthesis by human liver myofibroblasts is inhibited by α2-macroglobulin
AM Tiggelman, C Linthorst, W Boers, HS Brand, RA Chamuleau |
Journal of Hepatology | 1997 |
Insulin-Like Growth Factors Stimulate Expression of Hepatocyte Growth Factor But Not Transforming Growth Factor β1 in Cultured Hepatic Stellate Cells*
S Skrtic, V Wallenius, S Ekberg, A Brenzel, AM Gressner, JO Jansson |
Endocrinology | 1997 |
In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features
V Paradis, P Mathurin, M Kollinger, F Imbert-Bismut, F Charlotte, A Piton, P Opolon, A Holstege, T Poynard, P Bedossa |
Journal of clinical pathology | 1997 |
Iron overload and liver fibrosis
MJ Arthur |
Journal of Gastroenterology and Hepatology | 1996 |
Transforming growth factor β (TGF-β) expression in isolated and cultured rat hepatocytes
C Gao, G Gressner, M Zoremba, AM Gressner |
Journal of Cellular Physiology | 1996 |
Role of transforming growth factor-[beta]1 in inhibiting endothelial cell proliferation in experimental alcoholic liver disease
AA Nanji, SR Tahan, M Golding, S Khwaja, A Rahemtulla, EN Lalani |
The American Journal of Pathology | 1996 |
Kupffer cells and pit cells are not effective in the defense against experimentally induced colon carcinoma metastasis in rat liver
P Griffini, SM Smorenburg, IM Vogels, W Tigchelaar, CJ Noorden |
Clinical & Experimental Metastasis | 1996 |
Growth enhancement of implanted human colorectal cancer cells by the addition of fibroblastsin vivo
MC Loizidou, R Carpenter, H Laurie, AJ Cooper, P Alexander, I Taylor |
British Journal of Surgery | 1996 |
Histological features predictive of liver fibrosis in chronic hepatitis C infection
V Paradis, P Mathurin, A Laurent, F Charlotte, M Vidaud, T Poynard, C Hoang, P Opolon, P Bedossa |
Journal of clinical pathology | 1996 |
Drug-Induced Hepatotoxicity
RG Cameron, G Feuer, FA de la Iglesia |
1996 | |
Molecular and cellular aspects of iron-induced hepatic cirrhosis in rodents
A Pietrangelo, R Gualdi, G Casalgrandi, G Montosi, E Ventura |
Journal of Clinical Investigation | 1995 |
Molecular dissection of the mitogenic effect of hepatocytes on cultured hepatic stellate cells
AM Gressner, B Lahme, A Brenzel |
Hepatology | 1995 |
Transforming growth factor—beta 1 (TGF-β1) and TGF-β1 receptors in normal, cirrhotic, and neoplastic human livers
P Bedossa, E Peltier, B Terris, D Franco, T Poynard |
Hepatology | 1995 |
Novel insights into the biology and physiology of the Ito cell
M Pinzani |
Pharmacology & Therapeutics | 1995 |
Transforming growth factor-β1 regulates platelet-derived growth factor receptor β subunit in human liver fat-storing cells
M Pinzani, A Gentilini, A Caligiuri, RD Franco, G Pellegrini, S Milani, F Marra, P Gentilini |
Hepatology | 1995 |
Chronic ethanol consumption increases hepatic sinusoidal contractile response to endothelin-1 in the rat
M Bauer, NC Paquette, JX Zhang, I Bauer, BH Pannen, SR Kleeberger, MG Clemens |
Hepatology | 1995 |
Identification and characterization of a fibroblast marker: FSP1
F Strutz, H Okada, CW Lo, T Danoff, RL Carone, JE Tomaszewski, EG Neilson |
The Journal of Cell Biology | 1995 |
Quantitative analysis of transforming growth factor β1 messenger RNA in the liver of patients with chronic hepatitis C: Absence of correlation between high levels and severity of disease
D Roulot, H Durand, T Coste, J Rautureau, AD Strosberg, R Benarous, S Marullo |
Hepatology | 1995 |
Hepatic stellate (ITO) cells: expanding roles for a liver-specific pericyte
M Pinzani |
Journal of Hepatology | 1995 |
Acetalde hyde-Induced Stimulation of Collagen Synthesis and Gene Expression Is Dependent on Conditions of Cell Culture: Studies with Rat Lipocytes and Fibroblasts
JJ Maher, S Zia, C Tzagarakis |
Alcoholism, clinical and experimental research | 1994 |
Stimulation of collagen α1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: A link to tissue fibrosis?
P Bedossa, K Houglum, C Trautwein, A Holstege, M Chojkier |
Hepatology | 1994 |
Undulin RNA and protein expression in normal and fibrotic human liver
S Milani, C Grappone, G Pellegrini, D Schuppan, H Herbst, A Calabró, A Casini, M Pinzani, C Surrenti |
Hepatology | 1994 |
Feedback Mechanisms between ?2M and TGF?1 Reduce Extracellular Matrix Synthesis of Liver Fat-Storing Cells
MG Bachem, G Schüftan, P Schirrmacher, AM Gressner |
Annals of the New York Academy of Sciences | 1994 |
Enhancement of transforming growth factor β1 expression in the rat pancreas during regeneration from caerulein-induced pancreatitis
T Gress, F Müller-Pillasch, HP Elsässer, M Bachem, C Ferrara, H Weidenbach, M Lerch, G Adler |
European Journal of Clinical Investigation | 1994 |
Regulation of Proteoglycan Expression in Fibrotic Liver and Cultured Fat-Storing Cells
AM Gressner, N Krull, MG Bachem |
Pathology - Research and Practice | 1994 |
Prostaglandin E suppression of platelet-derived-growth-factor-induced Ito cell mitogenesis occurs independent of raf perinuclear translocation and nuclear proto-oncogene expression
DW Beno, UR Rapp, BH Davis |
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 1994 |
Perisinusoidal lipocytes and fibrogenesis
AM Gressner |
Gut | 1994 |
Hepatic lipocytes, TIMP-1 and liver fibrosis
M J Arthur, J P Iredale |
Journal of the Royal College of Physicians of London | 1994 |
Modulation of transforming growth factor beta receptors of rat lipocytes during the hepatic wound healing response. Enhanced binding and reduced gene expression accompany cellular activation in culture and in vivo
SL Friedman, G Yamasaki, L Wong |
The Journal of biological chemistry | 1994 |
Hepatocyte-conditioned medium potentiates insulin-like growth factor (IGF) 1 and 2 stimulated DNA synthesis of cultured fat storing cells
AM Gressner, A Brenzel, T Vomeyer |
Liver | 1993 |
Tumor necrosis factor alpha (TNFα) and transforming growth factor β1 (TGFβ1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts
MG Bachem, KM Sell, R Melchior, J Kropf, T Eller, AM Gressner |
Virchows Archiv B Cell Pathology Including Molecular Pathology | 1993 |
Retinoic acid suppresses the response to platelet-derived growth factor in human hepatic Ito-cell-like myofibroblasts: a post-receptor mechanism independent of raf/fos/jun/egr activation
BH Davis, D Coll, DW Beno |
Biochemical Journal | 1993 |
Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-β1 revealed byin situ hybridization during experimentally induced liver fibrosis in the rat
NB Krull, T Zimmermann, AM Gressner |
Hepatology | 1993 |
Confocal microscopy immunofluorescence localization of desmin and other intermediate filament proteins in fetal rat livers
J Vassy, JP Rigaut, D Briane, M Kraemer |
Hepatology | 1993 |
The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture
MG Bachem, D Meyer, W Schäfer, U Riess, R Melchior, KM Sell, AM Gressner |
Journal of Hepatology | 1993 |
In Vitro Biological Systems
GM Hawksworth, EM Cockburn, JG Simpson, PH Whiting |
In Vitro Biological Systems | 1993 |
Synergism between hepatocytes and Kupffer cells in the activation of fat storing cells (perisinusoidal lipocytes)
AM Gressner, S Lotfi, G Gressner, E Haltner, J Kropf |
Journal of Hepatology | 1993 |
Modulation of perisinusoidal cell cytoskeletal features during experimental hepatic fibrosis
A Schmitt-Gräff, G Chakroun, G Gabbiani |
Virchows Archiv A Pathological Anatomy and Histopathology | 1993 |
Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver
JP Iredale, G Murphy, RM Hembry, SL Friedman, MJ Arthur |
Journal of Clinical Investigation | 1992 |