Role of microRNAs in Alcohol-Induced Multi-Organ Injury

Abstract

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption.

Keywords: alcoholic liver disease; alcoholic pancreatitis; alcoholism; lncRNA; miRNA; teratogen.

Figure 1

Ethanol Induces Damage to Vital Organs in the Human Body. Ethanol consumption induces liver cells to accumulate lipid droplets and predisposes to alcoholic steatohepatitis, cirrhosis and increases the risk for the development hepatocellular carcinoma. In the pancreas, chronic alcohol consumption results in pancreatitis and pancreatic fibrosis. In the intestine, ethanol induces epithelial barrier dysfunction and gram negative bacterial overgrowth resulting in an enhanced production of LPS for the pathogenesis of alcoholic liver injury. Ethanol also produces brain damage by altering hippocampus structure and function and neuronal loss. Chronic ethanol consumption also causes alcoholic cardiomyopathy and cardiac arrhythmias. Additionally, alcohol has been shown to act as a teratogenic agent and epigenetic modulator via altering non-coding RNA levels such as microRNA and lncRNAs.