Effect of High Concentrations of Fructose on the Expression of TGF-β and α-SMA Genes in Human Hepatic Stellate Cells

Abstract

Background: Liver fibrosis is a reversible response to wound-healing that occurs in most forms of chronic liver damage, beginning with the activation of hepatic stellate cells (HSCs). The increased expression of genes, such as beta-converting growth factor (TGF-β) and actin-alpha smooth muscle (α-SMA) indicates the activation of HSCs. During liver damage, HSCs are activated and converted to myofibroblasts. As a result, the expression of TGF-β and αSMA genes in HSCs increases and leads to liver fibrosis. High fructose intake is known to have harmful effects on human health. Due to the persistent increase in high fructose intake via many beverages and foods in industrialized countries, much concern has been raised about the effect of fructose on liver damage, but its role in activating human HSCs has not been studied. Objectives: We aimed to investigate the effect of high fructose concentration on human HSCs activation by measuring the level of mRNA expression of TGF-β and α-SMA genes involved in liver fibrosis. Methods: Human HSCs were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) plus 10% Fetal Bovine Serum (FBS) at 37°C in 5% CO2. Cells were incubated in media containing 25 and 30 mM fructose for 48 h. The control group was incubated in DMEM without fructose. The cells were serum-starved for 24 h before treatment. Then, the total RNA was extracted, reversely transcribed into cDNA, and underwent Quantitative Real-time PCR (qRT-PCR). Results: The results indicated that the mRNA expression of TGF-β and αSMA genes significantly increased by treating with 25 and 30 mM fructose in HSCs when compared to the control group (P < 0.05). Conclusions: The increase in the mRNA of TGF-β and αSMA genes is used as a standard marker for HSC activation, leading to liver fibrosis. The results demonstrated that high fructose concentration could activate HSCs and increase the levels of TGF-β and αSMA in these cells. Thus, controlling fructose consumption and identifying the mechanism of fructose action is important to treat and reduce liver injury.

LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease

“…This could be attributed to the activation of hepatic stellate cells by carbohydrates. Recent studies suggest that high carbohydrate intake directly activates these cells 53 – 55 , which play a crucial role in the development and progression of liver cirrhosis 56 . An in vitro study by Piras et al demonstrated that conditioned medium derived from hepatocytes treated with a combination of palmitate and fructose elicited a significantly greater degree of transcriptomic changes in hepatic stellate cells than conditioned medium from hepatocytes treated with palmitate alone 57 .…”