Roles of TGF-beta in hepatic fibrosis

Axel, M. Gressner

doi:10.2741/gressner

Cited by 485 publications

(204 citation statements)

References 105 publications

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“…[39][40][41][42] On the other hand, it is reported that the overexpression of TGF-b plays a pivotal role in the progression of fibrosis. 43,44 In the present study, hepatic expression levels of IFNs, HGF and TGF-b mRNAs were examined by RT-PCR ( Figure 6). IFN-g mRNA expression was observed 12, 24 and 48 h after the administration of baculovirus.…”

Section: Ifn Inductionmentioning

confidence: 99%

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

et al. 2008

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The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis. Gene Therapy (2008) 15, 990-997;

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Section: Ifn Inductionmentioning

confidence: 99%

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

et al. 2008

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“…TGF-b1 is the key mediator in human fibrogenesis [13]. In HSCs, TGF-b1 favors the transition to myofibroblast-like cells, stimulates the synthesis of ECM protein, and inhibits their degradation through TGF-b/Smad signaling pathway.…”

Section: Effect Of Hypoxia On Tgf-b1 and P-smad2mentioning

confidence: 99%

Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway

et al. 2006

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Hypoxia is a common environmental stress factor and is also associated with various physiological and pathological conditions such as fibrogenesis. The activation of hepatic stellate cells (HSCs) is the key event in the liver fibrogenesis. In this study, the behavior of human HSCs LX-2 in low oxygen tension (1% O 2 ) was analyzed. Upon hypoxia, the expression of HIF-1a and VEGF gene was induced. The result of Western blotting showed that the expression of a-SMA was increased by hypoxic stimulation. Furthermore, the expression of MMP-2 and TIMP-1 genes was increased. Hypoxia also elevated the protein expression of the collagen type I in LX-2 cells. The analysis of TGF-b/ Smad signaling pathway showed that hypoxia potentiated the expression of TGF-b1 and the phosphorylation status of Smad2. Gene expression profiles of LX-2 cells induced by hypoxia were obtained by using cDNA microarray technique.

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“…To date, TGF-␤1 has been the single most-studied potent activator of HSCs that is induced by liver insult and has been implicated in liver fibrogenesis. 34 Similar to FGF1 and FGF2, genomic ablation of TGF-␤1 depressed induction of hepatic matrix collagen ␣1(I) mRNA in response to injury. 23 To determine whether the induction of TGF-␤1 was deficient in FGF1(Ϫ/Ϫ)FGF2(Ϫ/Ϫ) livers, we compared the expression of TGF-␤1 mRNA in FGF1(Ϫ/ Ϫ)FGF2(Ϫ/Ϫ) livers to WT after acute CCl 4 administration.…”

Section: Normal Activation Of ␣-Sma and Tgf-␤1 Expression In Fgf1(ϫ/ϫmentioning

confidence: 99%

Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis

Wang

Jin

et al. 2003

The American Journal of Pathology

150

126

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Genomic ablation of hepatocyte-specific fibroblast growth factor receptor (FGFR)4 in mice revealed a role of FGF signaling in cholesterol and bile acid metabolism and hepatolobular restoration in response to injury without effect on liver development or hepatocyte proliferation. Although the potential role of all 23 FGF polypeptides in the liver is still unclear, the most widely studied prototypes, FGF1 and FGF2, are present and have been implicated in liver cell growth and function in vitro. To determine whether FGF1 and FGF2 play a role in response to injury and fibrosis, we examined the impact of both acute and chronic exposure to carbon tetrachloride (CCl 4 ) in the livers of FGF1-and FGF2-deficient mice. After acute CCl 4 exposure, FGF1(؊/؊)FGF2(؊/؊) mice exhibited an accelerated release of serum alanine aminotransferase similar to FGFR4 deficiency, but no effect on overall hepatolobular restoration or bile acid metabolism. The fibroblast growth factors (FGFs) comprise a family of 23 reported members that have varying affinities for variants of four different FGF receptor kinases (FGFR1 to FGFR4). 1-3 FGF1 and FGF2, the first two cloned members of the FGF family, 4,5 have received the most study, are widely expressed, and thus, predicted to be involved in tissue-specific functions and associated pathologies at their site of expression. 6,7 In vitro FGF1 affects cells of multiple origin whereas activity of FGF2 appears more limited to cells derived from mesenchyme and neuroectoderm. 8 FGF1 and FGF2 have been implicated in derivation of the liver from foregut endoderm. 9 However, mice lacking FGF1, FGF2, or both FGF1 and FGF2 are viable, fertile, and grossly indistinguishable from wild type (WT) except for modest defects in cardiovascular tissue, healing of skin wounds, and neuronal tissue. 3,10,11 This suggests that FGF1 and FGF2 alone are not essential for embryonic development or are compensated by other members of the extensive FGF ligand family. Consequently, FGF1-and FGF2-deficient animals are available for study of the role of the two factors in adult tissue homeostasis. Despite their ubiquity, little has emerged except for the modest effects of ablation of FGF1 and FGF2 in the cardiovascular, skin, and nervous systems.Although the levels of mRNA transcripts are low, longlived FGF1 and FGF2 polypeptides are present in the resting liver at significant levels. 12 This suggests that a significant reservoir of both ligands is present in the resting liver in an inactive state before activation and

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Roles of TGF-beta in hepatic fibrosis

Cited by 485 publications

References 105 publications

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

Hypoxia induces the activation of human hepatic stellate cells LX‐2 through TGF‐β signaling pathway

Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis

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