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Archives of biochemistry and biophysics

Archives of biochemistry and biophysics

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

Published:9 December 2024 DOI: 10.1016/j.abb.2024.110255 PMID: 39662717
Jianhui Xie,?Shiyan Chen,?Yangli Chen,?Junlu Tong,?Huijie Huang,?Jingwen Liao,?Jixin Sun,?Li Cong,?Yingjuan Zeng

Abstract

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.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Oleic acid 112-80-1 C18H34O2 1074 suppliers $5.00-$2148.30
Palmitic acid 57-10-3 C16H32O2 667 suppliers $5.00-$1166.55

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