FFA intervention on LO2 cells mediates SNX-10 synthesis and regulates MMP9 secretion in LX2 cells via TGF-β1.

作者：Jianhui Xie, Shiyan Chen, Yangli Chen, Jun Tong, Huijie Huang, Jingwen Liao, Jixin Sun, Li Cong, Yingjuan Zeng · 发表于：Archives of Biochemistry and Biophysics · 年份：2024 · DOI：10.1016/j.abb.2024.110255 · 研究领域：Medicine

BACKGROUND Metabolic-associated fatty liver disease (MAFLD) is a public health concern. Transforming growth factor-β1(TGF-β1) plays an important regulatory role in multiple MAFLD stages, as it can promote the expression of matrix metalloproteinase-9 (MMP9) and promote liver fibrosis. Sorting nexin protein-10 (SNX-10) may be involved in the occurrence and development of fatty liver disease. METHODS Free fatty acids (FFA) treatment was used to simulate the cellular lipid deposition stage of MAFLD and the interactions between cells were simulated via LX2 and LO2 coculture. The molecular interaction between the two cell types was studied via ELISA, immunoprecipitation, qPCR, and western blotting. RESULTS In FFA-treated LO2 cells, intracellular TGF-β1 expression increased as lipid deposition increased. FFA-treated LO2 cells promoted the expression and secretion of MMP9 by LX2 cells through paracrine pathways. MMP9 secretion decreased with decreasing SNX-10 expression in LX2 cells. The interaction between MMP9 and SNX-10 was confirmed by coimmunoprecipitation. TGF-β1 promoted the synthesis of SNX-10 through the p38 MAPK pathway, and SNX-10 affected the secretion of MMP9 through protein interactions, thereby affecting the development of liver fibrosis. CONCLUSIONS FFA induced lipid deposition in LO2 cells, and TGF-β1 mediated the p38 MAPK pathway to promote SNX-10 synthesis and stimulate MMP9 secretion, thereby regulating the involvement of LX2 in the process of liver fibrosis...