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Citations to this article

Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.
M G Bachem, … , K M Sell, A M Gressner
M G Bachem, … , K M Sell, A M Gressner
Published January 1, 1992
Citation Information: J Clin Invest. 1992;89(1):19-27. https://doi.org/10.1172/JCI115561.
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Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.

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Abstract

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.

Authors

M G Bachem, D Meyer, R Melchior, K M Sell, A M Gressner

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B Saile, N Matthes, T Knittel, G Ramadori
Hepatology 1999
Alkohol und Alkoholfolgekrankheiten
MV Singer, S Teyssen
1999
Mechanisms of Hepatic Fibrosis
RC Benyon, MJ Arthur
Journal of Pediatric Gastroenterology & Nutrition 1998
Activated Rat Stellate Cells Express c-metand Respond to Hepatocyte Growth Factor to Enhance Transforming Growth Factor β1 Expression and DNA Synthesis
H Ikeda, S Nagoshi, A Ohno, M Yanase, H Maekawa, K Fujiwara
Biochemical and Biophysical Research Communications 1998
Effects of Lysophosphatidic Acid on Proliferation of Stellate Cells and Hepatocytes in Culture
H Ikeda, Y Yatomi, M Yanase, H Satoh, A Nishihara, M Kawabata, K Fujiwara
Biochemical and Biophysical Research Communications 1998
Identification, culture, and characterization of pancreatic stellate cells in rats and humans
MG Bachem, E Schneider, H Groß, H Weidenbach, RM Schmid, A Menke, M Siech, H Beger, A Grünert, G Adler
Gastroenterology 1998
Isoforms and splice variant of transforming growth factor β–binding protein in rat hepatic stellate cells
W Gong, S Roth, K Michel, AM Gressner
Gastroenterology 1998
Interferon gamma treatment prevents procollagen gene expression without affecting transforming growth factor-β1 expression in pig serum-induced rat liver fibrosis in vivo
I Sakaida, K Uchida, Y Matsumura, K Okita
Journal of Hepatology 1998
Subcellular localization of (latent) transforming growth factor β and the latent TGF-β binding protein in rat hepatocytes and hepatic stellate cells: Subcellular Localization of (Latent) Transforming Growth Factor β and the Latent TGF-β Binding Protein in Rat Hepatocytes and Hepatic Stellate Cells
S Roth-Eichhorn, K Kühl, AM Gressner
Hepatology 1998
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

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