Exercise-Induced Release of Pharmacologically Active Substances and Their Relevance for Therapy of Hepatic Injury.

Chronic liver disease (CLD) features constant parenchymal injury and repair together with an increasing hepatic impairment, finally leading to fibrosis and cirrhosis and a heightened risk of hepatocellular carcinoma (HCC). Closely related to the rise in obesity, the worldwide prevalence of nonalcoholic fatty liver disease, the most common form of CLD, has reached an epidemic dimension and is estimated to afflict up to 46% of the general population, including more than one out of three U.S.

Pharmacological Intervention in Hepatic Stellate Cell Activation and Hepatic Fibrosis.

The activation and transdifferentiation of hepatic stellate cells (HSCs) into contractile, matrix-producing myofibroblasts (MFBs) are central events in hepatic fibrogenesis. These processes are driven by autocrine- and paracrine-acting soluble factors (i.e.

Immunomodulatory effects of transforming growth factor-β in the liver.

Members of the transforming growth factor-β (TGF-β) family are potent regulatory cytokines that affect multiple cell types of the immune system mediating pro-inflammatory or anti-inflammatory responses. In the liver, TGF-β is produced by a multitude of non-parenchymal liver cells including hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), and dendritic cells (DCs) as well as natural killer (NK) T cells among other hepatic lymphocytes. The effect of TGF-β on other cells is highly versatile.