Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype

Andrea Perra, Marta Anna Kowalik, Monica Pibiri, Giovanna M. Ledda‐Columbano, Amedeo Columbano – 27 March 2009 – Triiodothyronine (T3), through interaction with its intracellular thyroid hormone receptors (TRs), influences various physiological functions, including metabolism, development, and growth. We investigated the effect of T3 and the selective TR‐β agonist GC‐1 in two models of hepatocarcinogenesis. Preneoplastic lesions were induced in F‐344 rats via a single dose of diethylnitrosamine, followed by a choline‐deficient (CD) diet for 10 weeks.

Natural killer T cells regulate the homing of chemokine CXC receptor 3‐positive regulatory T cells to the liver in mice

Tania Santodomingo‐Garzon, Jinglan Han, Tai Le, Yang Yang, Mark G. Swain – 27 March 2009 – Natural killer T (NKT) cells and regulatory T cells (Tregs) are both found within the liver and are known to exhibit immune regulatory functions. Hepatic NKT cells are activated early during inflammatory responses and release cytokines, including interferon gamma (IFN‐γ), which we speculated could regulate Treg recruitment to the liver.

CD133+ liver cancer stem cells from methionine adenosyl transferase 1A–deficient mice demonstrate resistance to transforming growth factor (TGF)‐β–induced apoptosis

Wei Ding, Marialena Mouzaki, Hanning You, Joshua C. Laird, Jose Mato, Shelly C. Lu, C. Bart Rountree – 27 March 2009 – Methionine adenosyltransferase (MAT) is an essential enzyme required for S‐adenosylmethionine biosynthesis. Hepatic MAT activity falls during chronic liver injury, and mice lacking Mat1a develop spontaneous hepatocellular carcinoma by 18 months. We have previously demonstrated that CD133+CD45− oval cells isolated from 16‐month‐old Mat1a−/− mice represent a liver cancer stem cell population.

Differential expression of lumican and fatty acid binding protein‐1: New insights into the histologic spectrum of nonalcoholic fatty liver disease

Michael Charlton, Kimberly Viker, Anuradha Krishnan, Schuyler Sanderson, Bart Veldt, A. J. Kaalsbeek, Michael Kendrick, Geoffrey Thompson, Florencia Que, James Swain, Michael Sarr – 27 March 2009 – The basis of hepatocellular injury and progressive fibrosis in a subset of patients with nonalcoholic fatty liver disease (NAFLD) is poorly understood. We sought to identify hepatic proteins that are differentially abundant across the histologic spectrum of NAFLD.

Abrogation of hepatic ATP‐citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor‐deficient mice

Qiong Wang, Lei Jiang, Jue Wang, Shoufeng Li, Yue Yu, Jia You, Rong Zeng, Xiang Gao, Liangyou Rui, Wenjun Li, Yong Liu – 27 March 2009 – Hepatic steatosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and a key component of obesity‐associated metabolic dysfunctions featuring dyslipidemia, insulin resistance, and loss of glycemic control. It has yet to be completely understood how much dysregulated de novo lipogenesis contributes to the pathogenic development of hepatic steatosis and insulin resistance.

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