The functional role of microRNAs in alcoholic liver injury

Abstract

The function of microRNAs (miRNAs) during alcoholic liver disease (ALD) has recently become of great interest in biological research. Studies have shown that ALD associated miRNAs play a crucial role in the regulation of liver-inflammatory agents such as tumour necrosis factor-alpha (TNF-α), one of the key inflammatory agents responsible for liver fibrosis (liver scarring) and the critical contributor of alcoholic liver disease. Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is responsible for TNF-α release by Kupffer cells. miRNAs are the critical mediators of LPS signalling in Kupffer cells, hepatocytes and hepatic stellate cells. Certain miRNAs, in particular miR-155 and miR-21, show a positive correlation in up-regulation of LPS signalling when they are exposed to ethanol. ALD is related to enhanced gut permeability that allows the levels of LPS to increase, leads to increased secretion of TNF-α by the Kupffer cells and subsequently promotes alcoholic liver injury through specific miRNAs. Meanwhile, two of the most frequently dysregulated miRNAs in steatohepatitis, miR-122 and miR-34a are the critical mediators in ethanol/LPS activated survival signalling during ALD. In this review, we summarize recent findings regarding the experimental and clinical aspects of functions of specific microRNAs, focusing mainly on inflammation and cell survival after ethanol/LPS treatment, and advances on the role of circulating miRNAs in human alcoholic disorders.

Structure, Function and Metabolism of Hepatic and Adipose Tissue Lipid Droplets: Implications in Alcoholic Liver Disease

“…Excellent review articles discussing ethanol-induced alterations in miRs and their role in pathogenesis of liver injury have been published recently [136, 137]. However, the mode of ethanol delivery by oral feeding or gavage appears to modulate miRs differently [138, 139].…”

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common causes of liver disorders. Both metabolic changes and inflammatory pathways are altered in these patients (10,17,18,109,113,116,120). Patients with NASH committed to inflammation early in the disease and continue to have progressive inflammation over time, leading to fibrogenesis and liver cirrhosis.…”

“…Plasma Cer levels were increased during lipid infusion in humans and rats as well as in obese, insulin-resistant mice (142,176,180). Balanced diet deficiency in both methionine (MD) and choline (CD) are the common models of steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis (113,143,117). The MD diet is associated with weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD results in steatosis (29,31,73).…”

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Studies have shown that differentially expressed ncRNAs in the liver are associated with several physiological and pathological processes [206][207][208][209][210]. Some reports have suggested that ncRNAs could improve hepatocyte proliferation or induce the differentiation of stem cells into hepatocyte-like cells (Table 1).…”