Calcium Ionophore I Focal adhesion kinase FAK is
Focal adhesion kinase (FAK) is a non-receptor type tyrosine kinase that can further cooperatively interact with receptor tyrosine kinase signaling to regulate adhesion, migration, survival, proliferation, polarization, and differentiation . Following activation, phosphorylated extracellular regulated protein kinases (ERK) could translocate to the nucleus and activate transcription factors that are involved in response to mechanical stimulation. Reported in the literature is also an important signaling molecule in the inflammatory response, while the inflammatory reaction is closely related to fatty liver .
Although many studies explored the process of capillarization of liver sinusoids, the mechanism are still kept unclear. Based on our previous studies of effect on hepatic sinusoidal endothelialization induced under high Calcium Ionophore I and ox-LDL . In this study, we investigated the relationship between integrin αvβ5, FAK, ERK, VN and functional disfunction of LSECs under high glucose/ox-LDL conditions with inhibitors or not and to determinates the mechanism on the indexes in vivo and vitro.
Materials and methods
Statistics Data are expressed as mean ± standard deviation (±SD). Statistical comparisons between groups were made by analysis of one-way ANOVA followed by the LSD. All instructives were performed using the SPSS21.0. A value of P < 0.05 was considered statistically significant.
Discussion The occurrence of diabetic fatty liver is closely related to the impairment of glycolipid toxicity in diabetic liver vascular injury . T2DM is an independent risk factor of NAFLD, disorder of glycolipid metabolism is the common pathological basis of T2DM and NAFLD. As is reported previously that the occurrence and development of NAFLD is related to liver microcirculation dysfunction caused by hepatic sinusoidal capillarization . Liver microcirculation is an important site for hepatic lipid metabolism, in addition, liver sinusoid microcirculation dysfunction can cause hepatic lipid exchange disorders and ischemic injury of liver tissue, thereby affecting hepatocyte lipid metabolism, and promote and aggravate the formation of fatty liver [3,16]. Hepatic sinusoidal endothelial cells have no basement membranes but have many sinusoidal endothelial fenestrations in their membranes. Collagen type IV, VN, laminin and fibronectin contribute to the formation of the liver basement membrane of the main material, in which VN played a very important and irreplaceable role . Hyperglycemia, ox-LDL can induce LSECs dysfunction and promote hepatic sinusoidal capillarization, permanent hyperglycemia and recurrent circulation of oxLDL in diabetic patients are recognized as two important pathogenic products that cause diabetes to be damaged and inflammatory response, and induce diabetic vascular lesions and other complications . The establishment of T2DM + NAFLD rats in this study aims to investigate the effect of αvβ5 on hepaticsinus function. We confirmed that αvβ5 maybe play an important role in diabetic fatty liver disease from two aspects of the animal and cell for the first time. One of the pathological processes of NAFLD is hepatic sinusoidal capillarization, while formation of basement membrane is characteristics of hepatic sinusoidal capillarization. VN, a common basement membrane formation markers, which in the process of hepatic steatosis LSECs VN expression of vascular endothelial markers gradually enhanced but rarely express in normal LSECs . A recent study found that newly isolated LSECs express VN intracellularly while cultured LSECs takes shape a surface expression. Scanning electron microscopy was used to observe the end of the surface of LSECs obtained through VN magnetic bead sorting, suggesting that the expression of VN is closely related to the pore state of LSECs. The results of our study showed that the VN positive staining area and staining degree in the liver of T2DM rats were closely related to the fenestra, the expression of VN in the hepatic sinus endothelial gradually increased with fenestra, and the expression was the most significant in T2DM + NAFLD rats.