Abstract

The long-term objective of this project is to delineate the role of various cytokines in acute liver injury, regeneration, and repair. The following questions will be addressed. (1) What is the role of transforming growth factor-Beta (TGF-Beta) and tumor necrosis factor (TNF) in acute hepatic damage, regeneration and repair? This work will involve the examination of two models of acute liver injury, CC1 4 and galactosamine-induced liver damage, and regeneration after partial hepatectomy. Changes in TGF-Beta and TNF gene expression will be analyzed by Northern blot hybridizations and nuclear run-on assays, and protein levels quantitated as well. (2) What are the effects of inhibiting the actions of TGF-Beta and TNF? TGF- Beta and TNF blocking antibodies will be administered to the animal models which will then be studied for changes in histology, gene expression, or survivability. (3) How do prostaglandin PGE 2 and dexamethasone affect liver injury and repair? PGE 2 and dexamethasone will be used in the in vivo models to determine these agents effects on acute liver injury and repair. By achieving these aims a better understanding of the mechanisms of acute liver injury and repair will exist. With this basic knowledge, proper therapeutic modalities for this entity will become apparent.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK041296-02
Application #
3876262
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Wang, Tony Y; Portincasa, Piero; Liu, Min et al. (2018) Mouse models of gallstone disease. Curr Opin Gastroenterol 34:59-70
Hodge, Dayle Q; Cui, Jihong; Gamble, Matthew J et al. (2018) Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing Epithelial-Mesenchymal Transition. Sci Rep 8:841
Sharma, Yogeshwar; Liu, Jinghua; Kristian, Kathleen E et al. (2018) In Atp7b-/- Mice Modeling Wilson's Disease Liver Repopulation with Bone Marrowderived Myofibroblasts or Inflammatory Cells and not Hepatocytes is Deleterious. Gene Expr :
Stepankova, Martina; Bartonkova, Iveta; Jiskrova, Eva et al. (2018) Methylindoles and Methoxyindoles are Agonists and Antagonists of Human Aryl Hydrocarbon Receptor. Mol Pharmacol 93:631-644
Walters, Ryan O; Arias, Esperanza; Diaz, Antonio et al. (2018) Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. Cell Rep 25:663-676.e6
Liu, Zhongbo; Apontes, Pasha; Fomenko, Ekaterina V et al. (2018) Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics. Int J Mol Sci 19:
Tekirdag, Kumsal; Cuervo, Ana Maria (2018) Chaperone-mediated autophagy and endosomal microautophagy: Joint by a chaperone. J Biol Chem 293:5414-5424
Zhao, Rongbao; Najmi, Mitra; Aluri, Srinivas et al. (2018) Concentrative Transport of Antifolates Mediated by the Proton-Coupled Folate Transporter (SLC46A1); Augmentation by a HEPES Buffer. Mol Pharmacol 93:208-215
Amengual, Jaume; Guo, Liang; Strong, Alanna et al. (2018) Autophagy Is Required for Sortilin-Mediated Degradation of Apolipoprotein B100. Circ Res 122:568-582
Schneider, Michael; Kumar, Vivek; Nordstrøm, Lars Ulrik et al. (2018) Inhibition of Delta-induced Notch signaling using fucose analogs. Nat Chem Biol 14:65-71

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