Sp1 and Sp3 transcription factors mediate leptin-induced collagen α1(I) gene expression in primary culture of male rat hepatic stellate cells.

Mechanisms by which leptin stimulates collagen α(1)(I) [Col1a(I)] gene expression are unclear. The purposes of this study were to identify the trans-acting factors and cis-acting elements in Col1a(I) promoter involved in this effect as well as the pathways that are implicated. In primary cultures of rat hepatic stellate cells (HSCs), we measured the effects of leptin on Col1a(I) gene and protein expression and on the binding of nuclear proteins to the Col1a(I) promoter.

Protein-tyrosine phosphatases are involved in interferon resistance associated with insulin resistance in HepG2 cells and obese mice.

Insulin resistance is a risk factor for non-response to interferon/ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine the role played by protein-tyrosine phosphatases (PTPs) in the absence of interferon-α (IFNα) response associated with insulin resistance. We induced insulin resistance by silencing IRS-2 or by treating HepG2 cells with tumor necrosis factor-α (TNFα) and analyzed insulin response by evaluating Akt phosphorylation and IFNα response by measuring Stat-1 tyrosine phosphorylation and 2',5'-oligoadenylate synthase and myxovirus resistance gene expression.

Melatonin improves mitochondrial respiratory chain activity and liver morphology in ob/ob mice.

In previous studies, we have shown that mitochondrial respiratory chain (MRC) activity is decreased in patients with nonalcoholic steatohepatitis and in ob/ob mice and that peroxynitrite plays a pathogenic role. The present study examined whether melatonin, a peroxynitrite scavenger, prevents: (i) the in vitro effects of peroxynitrite on normal mitochondrial proteins and (ii) the development of nonalcoholic liver disease, MRC dysfunction and proteomic changes found in the mitochondrial complexes from ob/ob mice. We studied MRC activity, assembly of mitochondrial complexes and its subunits in normal mitochondrial proteins exposed to peroxynitrite in the absence and presence of melatonin.

Fibronectin increases survival of rat hepatic stellate cells--a novel profibrogenic mechanism of fibronectin.

Unlabelled: The aims of this study were to determine whether fibronectin increases survival of hepatic stellate cells (HSCs) in starving conditions, and to identify the signal transduction pathways involved in this effect.

Methods: Primary culture of rat HSCs were plated on fibronectin-uncoated or coated culture wells, and grown in the presence of 0.2% or 20% fetal calf serum.