High glucose regulates LN expression in human liver sinusoidal endothelial cells through ROS/integrin αvβ3 pathway

摘要

Diabetes mellitus can cause a wide variety of vascular complications and is one of the major risk factors for Non Alcoholic Fatty Liver Disease (NAFLD). The present study was designed investigate the expression of laminin (LN) in human liver sinusoidal endothelial cells (HLSECs) induced by high glucose and the role of reactive oxygen species (ROS) and integrin αvβ3 in the regulation of LN expression. HLSECs were cultured and treated with media containing 25 mM glucose in the presence or absence of N-acetylcysteine (NAC) or clone LM609. The level of intracellular ROS of HLSECs was measured with 2′,7′ dichloro-fluorescein diacetate (DCFH-DA) probe. Expression of integrin αvβ3 was measured using RT-PCR and Western blot. Expression of LN was testified by immunofluorescence assay. Compared with that in control group, ROS level and the expression of integrin αvβ3 and LN increased in high glucose group. Compared with that in high glucose group, antioxidant NAC inhibited the expression of integrin αvβ3, NAC and the anti-body for blocking integrin αvβ3 (clone LM609) down-regulated the expression of LN. However, the above parameters did not differ between control and mannitol groups. High glucose up-regulates expression of LN in HLSECs through ROS/integrin αvβ3 pathway.