Characterization and regulation of insulin-like growth factor binding proteins in human hepatic stellate cells.


:Cultured hepatic stellate cells (HSCs), the cell type primarily involved in the progression of liver fibrosis, secrete insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) activity. IGF-I exerts a mitogenic effect on HSCs, thus potentially contributing to the fibrogenic process in an autocrine fashion. However, IGF-I action is modulated by the presence of specific IGFBPs that may inhibit and/or enhance its biologic effects. Therefore, we examined IGFBP-1 through IGFBP-6 mRNA and protein expression in HSCs isolated from human liver and activated in culture. Regulation of IGFBPs in response to IGF-I and other polypeptide growth factors involved in the hepatic fibrogenic process was also assessed. RNase protection assays and ligand blot analysis demonstrated that HSCs express IGFBP-2 through IGFBP-6 mRNAs and release detectable levels of IGFBP-2 through IGFBP-5. Because IGF-I, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-beta (TGF-beta) stimulate HSC proliferation and/or matrix production, we tested their effect on IGFBPs released by HSCs. IGF-I induced IGFBP-3 and IGFBP-5 proteins in a time-dependent manner without an increase in the corresponding mRNAs. IGFBP-4 protein levels decreased in response to IGF-I. TGF-beta stimulated IGFBP-3 mRNA and protein but decreased IGFBP-5 mRNA and protein. In contrast, PDGF-BB failed to regulate IGFBPs compared with controls. Recombinant human IGFBP-3 (rhIGFBP-3) was then tested for its effect on IGF-I-induced mitogenesis in HSCs. rhIGFBP-3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner, with a peak effect observed at 25 nM IGFBP-3. Because TGF-beta is highly expressed in cirrhotic liver tissue, we determined whether IGFBP-3 mRNA expression is increased in liver biopsies obtained from patients with an active fibroproliferative response due to viral-induced chronic active hepatitis. In the majority of these samples, IGFBP-3 mRNA was increased compared with normal controls. These findings indicate that human HSCs, in their activated phenotype, constitutively produce IGFBPs. IGF-I and TGF-beta differentially regulate IGFBP-3, IGFBP-4, and IGFBP-5 expression, which, in turn, may modulate the in vitro and in vivo action of IGF-I.


J Cell Physiol


Gentilini A,Feliers D,Pinzani M,Woodruff K,Abboud S




Has Abstract


1998-02-01 00:00:00














  • Local effects of EGF, alpha-TGF, and EGF-like growth factors on lobuloalveolar development of the mouse mammary gland in vivo.

    abstract::Five-week-old female mice supplemented with estradiol and progesterone are able to respond to epidermal growth factor (EGF) and EGF-like growth factors (alpha-transforming growth factor [alpha-TGF] and crude mammary-derived growth factor) with local lobuloalveolar development when these growth factors are directly int...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Vonderhaar BK

    更新日期:1987-09-01 00:00:00

  • Transcription of ribosomal RNA is differentially controlled in resting and growing BALB/c 3T3 cells.

    abstract::Shortly after serum-deprived BALB/c 3T3 fibroblasts are stimulated to grow in medium containing 10% calf serum, the RNA polymerase I activity in permeabilized cells shows a two-fold increase over the values observed in either serum-deprived or density-inhibited resting cells. Inhibition of protein synthesis by pactamy...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Perrone-Bizzozero N,Iapalucci-Espinoza S,Medrano EE,Franze-Fernández MT

    更新日期:1985-07-01 00:00:00

  • Phenotypic effects of aldosterone and dexamethasone in a SV40-transformed mammalian cortical ascending limb cell line exhibiting mineralocorticoid receptors.

    abstract::We have analyzed the functional and morphological effects of corticosteroid hormones in a SV40-transformed rabbit cortical-ascending-limb (CAL) cell line (RC.SV2, Vandewalle et al., 1989) having mineralocorticoid (MR) and glucocorticoid (GR) receptors (Rafestin-Oblin et al., 1993). Both aldosterone and dexamethasone (...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Vandewalle A,Rafestin-Oblin ME,Hagege J,Géniteau-Legendre M,Cassingéna R,Ronco PM

    更新日期:1993-08-01 00:00:00

  • Bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from hypoxia/reoxygenation-induced injury through Notch2/mTOR/autophagy signaling.

    abstract::Bone marrow mesenchymal stem cells (BMSC) can ameliorate ischemic injury of various tissues. However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC-derived conditioned medium (BMSC-CM) on hypoxia/reoxygenation (H/R)-induced injury of H9c2 myocardi...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Li X,Xie X,Yu Z,Chen Y,Qu G,Yu H,Luo B,Lei Y,Li Y

    更新日期:2019-08-01 00:00:00

  • Absence of K-Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts.

    abstract::The involvement of Ras-GTPases in the development of renal fibrosis has been addressed in the last decade. We have previously shown that H- and N-Ras isoforms participate in the regulation of fibrosis. Herein, we assessed the role of K-Ras in cellular processes involved in the development of fibrosis: proliferation, m...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Muñoz-Félix JM,Fuentes-Calvo I,Cuesta C,Eleno N,Crespo P,López-Novoa JM,Martínez-Salgado C

    更新日期:2016-10-01 00:00:00

  • The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation.

    abstract::The tuftelin protein isoforms undergo post-translation modifications, and are ubiquitously expressed in various tissues in embryos, adults, and tumors. Developmental and pathological studies suggested an apparent correlation between oxygen deprivation and tuftelin expression. The aim of the study was therefore to inve...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Leiser Y,Silverstein N,Blumenfeld A,Shilo D,Haze A,Rosenfeld E,Shay B,Tabakman R,Lecht S,Lazarovici P,Deutsch D

    更新日期:2011-01-01 00:00:00

  • Decreased in vivo and in vitro colony stimulating activity responses to bacterial lipopolysaccharide in C3H/HeJ mice.

    abstract::Mice of the C3H/HeJ strain exhibit low inflammatory and immunological responses to certain bacterial lipopolysaccharide (LPS) preparations. Lymphocytes from C3H/HeJ mice also show defective LPS-induced mitogenesis. We tested the colony stimulating activity (CSA) response of C3H/HeJ mice. As controls we used mice of th...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Russo M,Lutton JD

    更新日期:1977-08-01 00:00:00

  • RGS2 regulates urotensin II-induced intracellular Ca2+ elevation and contraction in glomerular mesangial cells.

    abstract::Urotensin II (UII), a vasoactive peptide modulates renal hemodynamics. However, the physiological functions of UII in glomerular cells are unclear. In particular, whether UII alters mesangial tone remains largely unknown. The present study investigates the physiological effects of UII on glomerular mesangial cells (GM...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Adebiyi A

    更新日期:2014-04-01 00:00:00

  • Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway.

    abstract::Zearalenone is a mycotoxin produced mainly by Fusarium. There are numerous incidences of mycotoxicosis in laboratory and domestic animals, especially in pigs. However, little is known about molecular mechanisms of zearalenone toxicity. Granulosa cells are the maximal cell population in follicles, and they play an esse...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Zhu L,Yuan H,Guo C,Lu Y,Deng S,Yang Y,Wei Q,Wen L,He Z

    更新日期:2012-05-01 00:00:00

  • Induction of human malignant T-lymphoblastic cell lines MOLT-3 and jurkat by 12-O-tetradecanoylphorbol-13-acetate: biochemical, physical, and morphological characterization.

    abstract::The process of induction of human malignant T-lymphoblastic cell line MOLT-3 by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined. It was found that the induction process by TPA, which included increase in cells with receptors to sheep red blood cells (E--rosette positive--E+) and decrease in t...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Nagasawa K,Howatson A,Mak TW

    更新日期:1981-10-01 00:00:00

  • Induction of angiogenesis by smooth muscle cell-derived factor: possible role in neovascularization in atherosclerotic plaque.

    abstract::The development of atherosclerotic plaque is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of intraplaque hemorrhage. However, the mechanism and stimulus for neovascul...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Kuzuya M,Satake S,Esaki T,Yamada K,Hayashi T,Naito M,Asai K,Iguchi A

    更新日期:1995-09-01 00:00:00

  • Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells.

    abstract::Two important mediators of endothelium-dependent regulation of vascular smooth muscle tone and proliferation are nitric oxide (NO) and endothelin (ET-1). An imbalance between NO and ET-1 may contribute to the alterations in vascular tone characteristic of cardiovascular disease. The objective of this study was to dete...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Redmond EM,Cahill PA,Hodges R,Zhang S,Sitzmann JV

    更新日期:1996-03-01 00:00:00

  • Cleavage of the epidermal growth factor receptor by a membrane-bound leupeptin-sensitive protease active in nonionic detergent lysates of senescent but not young human diploid fibroblasts.

    abstract::Numerous studies suggest that epidermal growth factor (EGF) signaling is impaired in nonproliferating senescent human diploid fibroblasts downstream of receptor binding. One possible explanation for these results is that senescent cells possess unique enzymatic activities capable of regulating functional levels of the...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Carlin C,Phillips PD,Brooks-Frederich K,Knowles BB,Cristofalo VJ

    更新日期:1994-09-01 00:00:00

  • Phosphoinositide 3-kinase/Akt involvement in arsenic trioxide resistance of human leukemia cells.

    abstract::The purpose of this study was to evaluate the possible involvement of the phosphoinositide 3-kinase (PI3K)/Akt survival pathway in determining resistance to arsenic trioxide (As2O3)-induced apoptosis. We employed a HL60 cell clone (HL60AR) with a constitutively active PI3K/Akt survival pathway, as well as U937 and K56...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Tabellini G,Cappellini A,Tazzari PL,Falà F,Billi AM,Manzoli L,Cocco L,Martelli AM

    更新日期:2005-02-01 00:00:00

  • Localization of basic fibroblast growth factor to the developing capillaries of the bovine retina.

    abstract::The basic fibroblast growth factor (FGF) is a potent mitogen that has vascular endothelium as one of its principle target cells. Recent work has provided both the complete amino acid sequence of basic FGF and the nucleotide sequence of the genes for both human and bovine basic FGF. Although capillary endothelial cells...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Hanneken A,Lutty GA,McLeod DS,Robey F,Harvey AK,Hjelmeland LM

    更新日期:1989-01-01 00:00:00

  • A model for diabetic nephropathy: advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse.

    abstract::We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Igamma) transgenic (Tg) mice. The ICER Igamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta cells. Here in a longitudinal study we further anal...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Inada A,Kanamori H,Arai H,Akashi T,Araki M,Weir GC,Fukatsu A

    更新日期:2008-05-01 00:00:00

  • Ontogeny of human neutrophil granulocyte alkaline phosphatase.

    abstract::Human embryonic neutrophils (N) in the liver (from 8.5 mm crown-rump length) are alkaline phosphatase (AP) negative during the first trimester of pregnancy. Early bone marrow granulocytes (from eleventh to sixteenth weeks of gestation) behave similarly. Only a small percentage of slightly AP positive cells could be fo...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Kelemen E,Gulya E,Vass K

    更新日期:1978-06-01 00:00:00

  • Lipid A, the active part of bacterial endotoxins in inducing serum colony stimulating activity and proliferation of splenic granulocyte/macrophage progenitor cells.

    abstract::An analysis of which component of lipopolysaccharides (LPS), the lipid or the polysaccharide (PS), is active in stimulating the murine granulopoietic system has been performed. LPS with different structures, isolated from different mutant strains of Salmonella and chemical degradation products of lipopolysaccharides h...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Apte RN,Galanos C,Pluznik DH

    更新日期:1976-01-01 00:00:00

  • Platelet-derived growth factor-induced disruption of gap junctional communication and phosphorylation of connexin43 involves protein kinase C and mitogen-activated protein kinase.

    abstract::Previously we showed a rapid and transient inhibition of gap junctional communication (GJC) by platelet-derived growth factor (PDGF) in T51B rat liver epithelial cells expressing wild-type platelet-derived growth factor beta receptors (PDGFrbeta). This action of PDGF correlated with the hyperphosphorylation of the gap...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Hossain MZ,Ao P,Boynton AL

    更新日期:1998-08-01 00:00:00

  • Elevation of a potassium current in differentiating human leukemic (HL-60) cells.

    abstract::Human promyelocytic leukemia (HL-60) cells display a novel voltage-dependent outward current under voltage clamp. This current is present at low levels in the proliferative state and in granulocytes derived from HL-60 cells which were induced to differentiate with retinoic acid. It is elevated in macrophages derived f...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Wieland SJ,Chou RH,Chen TA

    更新日期:1987-08-01 00:00:00

  • Early changes in the membrane of HeLa cells adsorbing Sendai virus under conditions of fusion.

    abstract::Adsorption of Sendai virus at high multiplicity (500-1,000 HAU/10(6) cells) to HeLa cells grown in monolayers causes immediate changes in the ion barrier of the cell membrane, as well as changes in the morphology of the virus-treated cells. Within minutes of adsorption the cells begin to lose potassium and an extensiv...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Spiegelstein PF,Haimsohn M,Gitelman J,Kohn A

    更新日期:1978-05-01 00:00:00

  • Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP-2.

    abstract::The roles of Sonic hedgehog (Shh) and Bone morphogenetic protein-2 (Bmp-2) in osteoblast differentiation were investigated using in vitro cell systems. Recombinant amino-terminal portion of SHH (rSHH-N) dose dependently stimulated ALP activity in C3H10T1/2 and MC3T3-E1 cells. rSHH-N induced expression of Osteocalcin m...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Yuasa T,Kataoka H,Kinto N,Iwamoto M,Enomoto-Iwamoto M,Iemura S,Ueno N,Shibata Y,Kurosawa H,Yamaguchi A

    更新日期:2002-11-01 00:00:00

  • Expression of parathyroid hormone-related protein in cells of osteoblast lineage.

    abstract::The expression of parathyroid hormone-related protein (PTHrP) was studied in a range of cell cultures representative of the osteoblast lineage and in rat calvarial sections. Primary newborn rat calvarial cells, a rat preosteoblastic cell line (UMR 201), a mouse stromal cell line (ST 2), a mouse calvaria-derived osteob...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Suda N,Gillespie MT,Traianedes K,Zhou H,Ho PW,Hards DK,Allan EH,Martin TJ,Moseley JM

    更新日期:1996-01-01 00:00:00

  • Control of alkaline phosphatase activity in C3H10T1/2 cells: role of retinoic acid and cell density.

    abstract::The enzyme alkaline phosphatase (AP) has been shown to be lost or inappropriately expressed during carcinogenesis in some tissues. Because retinoic acid (RA) appears to play a role in the normal regulation of the enzyme (RA up-regulates AP in a variety of cell types) we have suggested that altered AP expression in som...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Reese DH,Larsen RA,Hornicek FJ

    更新日期:1992-05-01 00:00:00

  • Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss.

    abstract::Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways are triggered by receptor ac...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Liu H,Dong Y,Gao Y,Zhao L,Cai C,Qi D,Zhu M,Zhao L,Liu C,Guo F,Xiao J,Huang H

    更新日期:2019-07-01 00:00:00

  • Inhibition of human methionine adenosyltransferase 1A transcription by coding region methylation.

    abstract::Two genes (MAT1A and MAT2A) encode for the essential enzyme methionine adenosyltransferase (MAT). MAT1A is silenced in hepatocellular carcinoma (HCC), and absence of MAT1A leads to spontaneous development of HCC in mice. Previous report correlated promoter methylation to silencing of MAT1A but definitive proof was lac...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Tomasi ML,Li TW,Li M,Mato JM,Lu SC

    更新日期:2012-04-01 00:00:00

  • Altering microtubule stability affects microtubule clearance and nuclear extrusion during erythropoiesis.

    abstract::Mammalian erythrocytes are highly specialized cells that have adapted to lose their nuclei and cellular components during maturation to ensure oxygen delivery. Nuclear extrusion, the most critical event during erythropoiesis, represents an extreme case of asymmetric partitioning that requires a dramatic reorganization...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Xie S,Yan B,Feng J,Wu Y,He N,Sun L,Zhou J,Li D,Liu M

    更新日期:2019-11-01 00:00:00

  • Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo.

    abstract::Connective tissue growth factor (CTGF) is a secreted, extracellular matrix-associated signaling protein that regulates diverse cellular functions. In vivo, CTGF is expressed in many tissues with highest levels in the kidney and brain. The purpose of this study was twofold; first, to localize CTGF in normal bone in viv...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Safadi FF,Xu J,Smock SL,Kanaan RA,Selim AH,Odgren PR,Marks SC Jr,Owen TA,Popoff SN

    更新日期:2003-07-01 00:00:00

  • c-Ha-rasEJ transfection of rat aortic smooth muscle cells induces epidermal growth factor responsiveness and characteristics of a malignant phenotype.

    abstract::Although the role of several protooncogenes, including sis, myc, and myb in the regulation of growth and differentiation of vascular cells has been examined in some detail, limited information is available on the contribution of ras genes to these processes. In the present studies the influence of oncogenic ras transf...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Sadhu DN,Lundberg MS,Burghardt RC,Ramos KS

    更新日期:1994-12-01 00:00:00

  • Culture-induced increase in acidic and basic fibroblast growth factor activities and their association with the nuclei of vascular endothelial and smooth muscle cells.

    abstract::The activity of acidic and basic fibroblast growth factor-like mitogens (aFGF, bFGF) extracted from cultured bovine aortic endothelial (BAEC) and rat aortic smooth muscle cells (SMC) was compared with that of freshly isolated cells from the same tissues. Extracts of subendothelial extracellular matrix (ECM) and cell l...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章


    authors: Speir E,Sasse J,Shrivastav S,Casscells W

    更新日期:1991-05-01 00:00:00