Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease.

Abstract

Golgi protein 73 (GP73) is upregulated in a variety of liver diseases, yet the detailed mechanism is poorly characterized. We analyzed GP73 in a retrospective cohort including 4211 patients with chronic liver disease (CLD) or hepatocellular carcinoma (HCC). The effect of deoxycholic acid (DCA) and nuclear factor-kappa B (NF-κB) on expression and release of GP73 in Huh-7 and SMMC7721 cells were studied. A mouse study was used to confirm our findings in vivo. A positive correlation was found between serum GP73 and total bile acid (TBA) in cirrhotic patients (r = 0.540, p < 0.001), higher than that in non-cirrhotic CLD (r = 0.318, p < 0.001) and HCC (r = 0.353, p < 0.001) patients. In Huh-7 and SMMC7721 cells, DCA upregulated the expression and release of GP73 in a dose- and time-dependent manner. After overexpressing NF-κB p65, the promoter activity, GP73 messenger RNA (mRNA) level, and supernatant GP73 level were increased. The promotion effect of DCA on GP73 release was attenuated after inhibiting the NF-κB pathway. Mutating the binding sites of NF-κB in the sequence of the GP73 promoter led to a declined promoting effect of DCA on GP73. The upregulation role of DCA in GP73 expression through the NF-κB pathway was confirmed in vivo. In addition, exposure to DCA caused disassembly of Golgi apparatus. In summary, DCA upregulates the expression and release of GP73 via activating the NF-κB pathway and destroying the Golgi structure.

• Authors: Danli Yang, Mingjie Yao, Ying Yan, Yanna Liu, Xiajie Wen, Xiangmei Chen, Fengmin Lu
• Journal: Biomolecules (Biomolecules) Vol. 11 Issue 2 (02 02 2021) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 33540642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bile Acids and Salts
• GOLM1 protein, human
• GP73 protein, mouse
• Membrane Proteins
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• Phosphoproteins
• Deoxycholic Acid
• Nfkb1 protein, mouse

Topics

• Adult
• Animals
• Bile Acids and Salts (metabolism)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Cell Line, Tumor
• Chronic Disease
• Deoxycholic Acid (metabolism, pharmacology)
• Female
• Fibrosis
• Gene Expression Profiling
• Humans
• Liver Cirrhosis (drug therapy, metabolism)
• Liver Diseases (drug therapy, metabolism)
• Liver Neoplasms (drug therapy, metabolism)
• Male
• Membrane Proteins (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• Middle Aged
• NF-kappa B p50 Subunit (biosynthesis)
• Phosphoproteins (biosynthesis)
• Retrospective Studies
• Up-Regulation