Preface [Hot topic: Molecular Mechanisms of Liver Injury (Executive Editor: Xiao-Ming Yin)]

The past century has witnessed rapid progresses in the understanding of human diseases. This has been the time when studies on the pathogenesis of diseases advance from the traditional gross anatomic-physiological approach to the molecular approach, hence the birth of the molecular medicine. The remarkable achievement in the molecular biology makes the transition possible, which has no doubt deepened our understanding and changed our approach to the treatment of the disease. This progress is particularly important for the study of liver injury. An organ with multiple complicated functions and anatomically equipped with the unique double circulation systems, liver is constantly exposed to and vulnerable to hypoxia, free radicals, toxic and infectious substances. A significant portion of liver diseases are resulted from injury from these insults. Acute injury, if not resolved properly, can evolve into long-term adverse complications that could lead to liver cancer, which has a notoriously malicious clinical course and an extremely poor survival rate. While traditional analysis of the etiology and pathogenesis of liver injury could classify it into groups of infectious, ischemic, chemical, or immunological nature, molecular analyses of the biochemical process and signaling network often identify multiple mechanisms involved in each disease identity classified by the traditional method. More importantly, similar molecular processes can be shared among different disease identities. For example, immunological destruction of viral infected-hepatocytes activates death receptorinitiated caspase cascade, mitochondria dysfunction and free radicals generation, all contributing to the final demise of the cell. However, the same molecular events are also present in liver injury caused by other etiologies, such as cholestasis, ethanol, ischemia / reperfusion or endotoxemia. Thus it becomes increasingly important to understand these molecular processes and their contribution to the initiation and evolution of the disease. It is from this point that we have edited this special issue of Current Molecular Medicine for the molecular mechanisms of liver injury. To emphasize the molecular approach for the investigation of various liver injuries, in addition to the traditional vertical way of describing selected liver injury, we have devoted significantly more pages to the common molecular mechanisms, thus providing a horizontal way to examine the molecular events in details as to how they are activated and regulated in physiological and pathological conditions. The cross point of this combined vertical and horizontal approach is naturally the focus of liver injury, i.e., the functional alternations and the demise of the hepatocyte, often in the form of apoptosis. The overview by Higuchi and Gores provides a panoramic view of the molecular mechanisms of liver injury, exemplifying this approach. With the focus on the outcome of the liver injury, we then trace the molecular mechanisms of how different stimulus leads to this process, via death receptor activation (Yin and Ding), free radicals and oxidative stress (Kessova and Cederbaum, Chen et al), mitochondria permeability transition (Kim et al), or peroxisome proliferator-stimulated metabolic alterations (Yu et al) etc. For each of them, we discuss the intracellular signaling pathways, the effector molecules and the controlling and regulatory mechanisms. These molecular events constitute the pathogenesis of the most common types of liver injury, including viral hepatitis (Nakamoto and Kaneko), inflammatory hepatitis (Tsutsui et al), ischemic / reperfusion liver injury (Kim et al), septic shock induced-liver failure (Yin and Ding, Chen et al), alcoholic liver disease (Kessova and Cederbaum) and non-alcoholic steatohepatitis (Yu et al). With the long-term adverse effects of liver injury in mind, we have also addressed the mechanism of hepatocarcinogenesis (Colemen, and Yu et al), which puts a full stop on the natural history of liver injury. By putting all these topics in a single issue of Current Molecular Medicine, we hope we can best present the impact of the progress being made in this field of live study and provide a broad and comprehensive view on the molecular mechanisms that are operated in the liver injury in an intertwined way. This may serves as a road map to a better understanding of the disease and to the development of better therapeutic agents.