Proteomic screening of saturated fatty acid-induced hepatocytes-derived exosomes.

Abstract

e13568 Background: Most countries continuously westernize and industrialize, the prevalence of NAFLD is expected to increase, which will greatly increase social and economic burden. Meanwhile, the trend that NAFLD acts as a main stream of liver diseases will be much emphasized with the eradication and/or effective control of viral hepatitis in the future. There are many studies indicated that lipotoxicity of hepatocyte plays an important role in the inflammation and hepatic injury during the progression of liver steatohepatitis and HCC. However, the extracellular vesicles (EVs) participate in intercellular signaling, tissue injury and repair, and matrix remodeling still unclear. Methods: In this research, we used hepatitis liver cells (Huh 7.5.1 and Hep-G2) and LX-2 cell lines (liver stellate cells, HSCs) with palmitic acid (PA) to study the cell inflammation/fibrosis response and exosome contents. Results: The Oil red lipid droplet cell stain result found the liver cells has produced higher fatty oil droplet than HSCs cells in the same PA dose. However, the inflammation cytokines (IL-6, TNF-α, and IL-1β) and fibrosis-related protein (α-SMA and COL1A1) only significant increasing in HSCs cells but not in liver cells after the PA treatment. Isolation of exosomes from PA-treated hepatocytes presenting the same effect on the activation of HSCs, which lead to significant expression of fibrosis markerα-SMA and COL1A1. Based on the finding, we further analyzed the exosomes from PA-treated hepatocytes by LC-MS analysis and found 6 proteins (CFHR-4, A2M, HBG, APOB, IG, DCTN1) presenting compare to un-treated liver cells. Conclusions: This study provide the released Hep-EVs have important roles in hepatocyte-to-HSC communication.