TAK1 deficient liver parenchymal cells with Rip3 double knockout TAK1LPC
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE45206 | GEO | 2013/05/01
SECONDARY ACCESSION(S): PRJNA193234
REPOSITORIES: GEO
Similar Datasets
Project description:Genomic copy number profiling of TAK1 deficient liver parenchymal cells with Rip3 double knockout Sample vs. Reference (pool of 4 normal liver tissues)
2013-05-01 | E-GEOD-45206 | biostudies-arrayexpress
Project description:TAK1 deficient liver parenchymal cells with Rip3 double knockout TAK1LPC
| PRJNA193234 | ENA
Project description:Comparison of the genomic copy number status of livers from wildtype mice (reference) with Tak1/Casp8 knockout mice or Tak1/LPC knockout mice or Tak1/LPC/RIP3 knockout mice.
2013-07-22 | E-MTAB-1559 | biostudies-arrayexpress
Project description:For years, the term apoptosis was used synonymously for programmed cell death. However, it was recently discovered that programmed necrosis M-bM-^@M-^S dependent on the kinases Receptor-Interacting-Protein-Kinase (RIP)1 and RIP3 (also called necroptosis) M-bM-^@M-^S represents a major programmed cell-death pathway in development and immunity. At present, the functions of necroptosis in hepatitis, liver cancer development and biliary disease are unclear. Here we show that in mice with chronic hepatitis due to conditional ablation of TGF-beta-activated kinase1 (TAK1) in liver parenchymal cells (LPC), both apoptotic and necroptotic signaling pathways are activated. Strikingly, only Caspase-8-dependent apoptosis promotes spontaneous liver cancer development, while in contrast LPC necroptosis inhibits hepatic tumourigenesis. The tumour-promoting effect of apoptosis results from an induction of strong compensatory proliferation of LPC, linked with the paracrine action of growth factors like Insulin-like growth factor-2 (IGF-2) not induced by necroptosis. In addition to prevention of HCC development, induction of necroptosis leads to massive cholestasis and hyperbilirubinemia, resulting from an insufficient ductular reaction and biliary regeneration from the hepatic stem cell niche as a response to chronic hepatitis. These results indicate previously undefined distinctive functions of apoptosis and programmed necrosis in controlling cancer development and cholestasis in the liver with important implications for future therapeutic strategies in chronic liver disease. 8 samples were analysed. We compared groups of 4 Tak1/Caspase8 LPC double knockout mice and 4 Tak1 LPC-KO/Rip3-/- mice to detect genes differentially regulated by apoptotic and necrotic signalling pathways.
2013-04-01 | E-GEOD-39750 | biostudies-arrayexpress
Project description:BCR-induced gene expression profile in wild-type and B cell-specific TAK1-deficient B cells; to elucidate how TAK1 regulates BCR-mediated proliferative response Keywords: ordered
2005-08-11 | GSE3065 | GEO
Project description:BCR-induced gene expression profile in wild-type and B cell-specific TAK1-deficient B cells; to elucidate how TAK1 regulates BCR-mediated proliferative response Experiment Overall Design: Purified splenic B cells (CD43 negative) were treated with or without anti-IgM (20 micloG/mL) for 4 h. Total RNA was extracted with an RNeasy kit (Qiagen), double-stranded DNA was synthesized from 10 micloG of total RNA with the SuperScript Choice System (Invitrogen) primed with T7-(dT) 24 primer. These cDNAs were used to prepare biotin-labeled cRNA by an in vitro transcription reaction performed using T7 RNA polymerase in the presence of biotinylated-ribonucleotides, according to the manufacturerâs protocol (Enzo Diagnostics). The cRNA product was purified using an RNeasy kit, fragmented, and hybridized to Affymetrix mouse expression array A430.2 microarray chips, according to the manufacturerâs protocol (Affymetrix). The hybridized chips were stained, washed, and scanned with a GeneArray Scanner (Affymetrix).
2008-06-12 | E-GEOD-3065 | biostudies-arrayexpress
Project description:The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis. TAK1-deficient (TAK1-/-) mice are resistant to the development of age- and high fat diet (HFD)-induced metabolic syndrome. Biochemical analysis showed significantly lower hepatic triglyceride levels and reduced lipid accumulation in adipose tissue in TAK1-/- mice compared to wild type (WT) mice. Gene expression profiling analysis revealed that the expression of several genes encoding proteins involved in lipid uptake and triglyceride synthesis and storage, including Cidea, Cidec, Mogat1, and CD36, was greatly decreased in the liver of TAK1-/- mice. Moreover, TAK1-/- mice exhibit reduced infiltration of inflammatory cells and expression of inflammatory genes in adipose tissue and were resistant to the development of glucose intolerance and insulin resistance. TAK1-/- mice consume more oxygen and produce more carbon dioxide than WT mice suggesting a higher rate of energy expenditure. Together, these results indicate that TAK1 plays a critical role in the regulation of energy and lipid homeostasis and potentiates the development of metabolic syndrome. Our study suggests that TAK1 might provide a novel therapeutic target in the management of metabolic syndrome.
2010-10-01 | GSE21903 | GEO
Project description:The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis. TAK1-deficient (TAK1-/-) mice are resistant to the development of age- and high fat diet (HFD)-induced metabolic syndrome. Biochemical analysis showed significantly lower hepatic triglyceride levels and reduced lipid accumulation in adipose tissue in TAK1-/- mice compared to wild type (WT) mice. Gene expression profiling analysis revealed that the expression of several genes encoding proteins involved in lipid uptake and triglyceride synthesis and storage, including Cidea, Cidec, Mogat1, and CD36, was greatly decreased in the liver of TAK1-/- mice. Moreover, TAK1-/- mice exhibit reduced infiltration of inflammatory cells and expression of inflammatory genes in adipose tissue and were resistant to the development of glucose intolerance and insulin resistance. TAK1-/- mice consume more oxygen and produce more carbon dioxide than WT mice suggesting a higher rate of energy expenditure. Together, these results indicate that TAK1 plays a critical role in the regulation of energy and lipid homeostasis and potentiates the development of metabolic syndrome. Our study suggests that TAK1 might provide a novel therapeutic target in the management of metabolic syndrome. For microarray liver total RNAs were purified from WT and TAK1 KO mice and applied on Agilent mouse genome chip. Liver from 1 year old- WT and TAK1 KO mice.
2010-09-30 | E-GEOD-21903 | biostudies-arrayexpress
Project description:In this study we show that TGFβ-activated kinase 1 (TAK1), is crucial for ensuring EC survival on TNFα stimulation. EC-specific TAK1-knockout in adult mice resulted in rapid death of the animal due to destruction of intestinal and liver blood vessels. TNFα from myeloid cells responding to intestinal microbiota was responsible for EC death in the intestine and liver. Our results illuminate mechanisms ensuring survival of intestinal and liver EC under physiological conditions
2019-01-11 | GSE115190 | GEO
Project description:To evaluate the effects of TAK1 inhibition on TGF-beta regulated fibrosis using a novel small molecule inhibitor of TAK1.
2023-05-17 | GSE232435 | GEO