Transcription factors ETF, E2F, and SP‐1 are involved in cytokine‐independent proliferation of murine hepatocytes

Sebastian Zellmer, Wolfgang Schmidt‐Heck, Patricio Godoy, Honglei Weng, Christoph Meyer, Thomas Lehmann, Titus Sparna, Wiebke Schormann, Seddik Hammad, Clemens Kreutz, Jens Timmer, Fritz von Weizsäcker, Petra A. Thürmann, Irmgard Merfort, Reinhard Guthke, Steven Dooley, Jan G. Hengstler, Rolf Gebhardt – 20 August 2010 – The cellular basis of liver regeneration has been intensely investigated for many years. However, the mechanisms initiating hepatocyte “plasticity” and priming for proliferation are not yet fully clear.

Interleukin‐6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice

Xiuying Zhang, Shingo Tachibana, Hua Wang, Masayuki Hisada, George Melville Williams, Bin Gao, Zhaoli Sun – 20 August 2010 – We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL‐6 knockout (KO) and wild‐type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8‐OHdG) in both IL‐6KO and WT mice.

Type 2 diabetes in mice induces hepatic overexpression of sulfatase 2, a novel factor that suppresses uptake of remnant lipoproteins

Keyang Chen, Ming‐Lin Liu, Lana Schaffer, Mingzhen Li, Guenther Boden, Xiangdong Wu, Kevin Jon Williams – 20 August 2010 – Type 2 diabetes mellitus (T2DM) impairs hepatic clearance of atherogenic postprandial remnant lipoproteins. Our work and that of others have identified syndecan‐1 heparan sulfate proteoglycans (HSPGs) as remnant lipoprotein receptors. Nevertheless, defects in the T2DM liver have not been molecularly characterized, and neither has the correction that occurs upon caloric restriction.

E‐cadherin antagonizes transforming growth factor β1 gene induction in hepatic stellate cells by inhibiting RhoA–dependent Smad3 phosphorylation

Il Je Cho, Young Woo Kim, Chang Yeob Han, Eun Hyun Kim, Richard A. Anderson, Young Sok Lee, Chang Ho Lee, Se Jin Hwang, Sang Geon Kim – 20 August 2010 – Cadherins mediate cell‐cell adhesion and catenin (ctn)‐related signaling pathways. Liver fibrosis is accompanied by the loss of E‐cadherin (ECAD), which promotes the process of epithelial‐mesenchymal transition. Currently, no information is available about the inhibitory role of ECAD in hepatic stellate cell activation.

The role of intestinal endotoxin in liver injury: A long and evolving history

James P. Nolan – 20 August 2010 – From the mid‐1950s, it was observed that liver injury by a variety of toxins greatly sensitized the host to the effects of administered lipopolysaccharide. In the nutritional cirrhosis of choline deficiency, and in acute toxic injury as well, the need for the presence of enteric endotoxin was demonstrated. The universality of this association was striking for almost all agents associated with liver injury.

Liver regeneration is impaired in lipodystrophic fatty liver dystrophy mice

Vered Gazit, Alexander Weymann, Eric Hartman, Brian N. Finck, Paul W. Hruz, Anatoly Tzekov, David A. Rudnick – 20 August 2010 – We previously reported that mice subjected to partial hepatectomy exhibit rapid development of hypoglycemia followed by transient accumulation of fat in the early regenerating liver. We also showed that disrupting these metabolic alterations results in impaired liver regeneration. The studies reported here were undertaken to further characterize and investigate the functional importance of changes in systemic adipose metabolism during normal liver regeneration.

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