0000000000039734

AUTHOR

Jürgen Henninger

showing 2 related works from this author

Hepatocellular expression of a dominant-negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis

2001

The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by redu…

MaleGenetically modified mouseCancer Researchmedicine.medical_specialtyCarcinoma HepatocellularTransgeneMice TransgenicProtein Serine-Threonine KinasesBiologymedicine.disease_causeMiceLiver Neoplasms ExperimentalTransforming Growth Factor betaInternal medicineGeneticsmedicineAnimalsRNA MessengerMolecular BiologyCells CulturedTissue homeostasisDNA synthesisReceptor Transforming Growth Factor-beta Type IICell biologyC-Reactive ProteinEndocrinologymedicine.anatomical_structureHepatocyteMutationHepatocytesSignal transductionCarcinogenesisReceptors Transforming Growth Factor betaTransforming growth factorOncogene
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TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis.

1999

Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-beta1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated form of TGF-beta1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-beta1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels reached600 ng/ml in transgenic animals, which is100 times above normal …

Genetically modified mouseLipopolysaccharidesmedicine.medical_specialtyTranscription GeneticPhysiologyTransgeneRecombinant Fusion ProteinsMice TransgenicBiologyRegulatory Sequences Nucleic AcidLiver Cirrhosis ExperimentalMiceDownregulation and upregulationFibrosisIn vivoTransforming Growth Factor betaPhysiology (medical)Internal medicinemedicineAnimalsHumansRNA MessengerPromoter Regions GeneticRegulation of gene expressionHepatologyGastroenterologymedicine.diseaseMolecular biologyImmunohistochemistryEndocrinologymedicine.anatomical_structureC-Reactive ProteinGene Expression RegulationLiverHepatocyteHepatic stellate cellCollagenProcollagen
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