Abstract
To investigate the roles of reactive oxygen species (ROS) and integrin αvβ3 in palmitate-induced laminin expression of human liver sinusoidal endothelial cells (HLSECs). The protein expression of integrin αv, integrin β3 and laminin are increased by palmitate in HLSECs in a time- and dose-dependent manner. NAC, the ROS inhibitor, significantly inhibited the up-regulation of protein expression of integrin αv, integrin β3 and laminin by palmitate (P < 0.05). Palmitate markedly enhanced ROS formation (P < 0.05), which was not inhibited by LM609, the antibody of integrin αvβ3. Palmitate significantly increased laminin synthesis (P < 0.05), which was attenuated by LM609 and NAC (P < 0.05). HLSECs were treated with palmitate in the presence or absence of LM609 (10 μg/ml) or N-acetylcysteine (NAC) (2 mM). Expression of integrin αv, integrin β3 and laminin were measured by RT-PCR and Western blot. Immunocytochemistry were used for examining laminin expression. The generation of ROS was measured using the fluorescent signal 2',7' dichloro-fluorescein diacetate (DCFH-DA). The results suggested that palmitate increases laminin expression through ROS/integrin αv/β3 pathway.
Highlights
With the increased incidence of diabetes, diabetic patients with non-alcoholic fatty liver disease (NAFLD) showed an increasing trend
The results suggested that palmitate increases laminin expression through reactive oxygen species (ROS)/integrin αv/β3 pathway
The results revealed that both mRNA and protein expression of integrin αv, integrin β3 and laminin increased in response to palmitate in a time- and dose-dependent manner with exception of the data at 200 μmol/L palmitate (Figure 1B, 1C, 1D; Figure 2 and Figure 5, Figure 6)
Summary
With the increased incidence of diabetes, diabetic patients with non-alcoholic fatty liver disease (NAFLD) showed an increasing trend. Capillarization of liver sinusoidals plays an important role in NAFLD process, whether diabetes could accelerate the occurrence of sinusoidal capillaries rarely reported. One of the most important saturated FFAs in human blood, induce oxidative stress and inflammatory response in endothelial cells. The walls are composed of human liver sinusoidal endothelial cells (HLSECs), which are connected loosely and conducive to the exchange of material between sinusoidal blood and liver cells. Researches had shown that sinusoidal capillarization can make the liver cells reduce the uptake of metabolites and oxygen, which result in the metabolism www.oncotarget.com disorders, subsequently leading to NAFLD [6]. Couvelard et al Have shown that absence of the basement membrane in normal liver may be a result of reduced expression of integrin and indicates that the integrin is upregulated during liver fibrosis. The vitronectin receptor, αvβ integrin, is highly expressed in endothelial cells of angiogenic vessels [8]
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