Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease
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 n...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2218-273X/11/2/205 |
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| author | Danli Yang Mingjie Yao Ying Yan Yanna Liu Xiajie Wen Xiangmei Chen Fengmin Lu |
| author_facet | Danli Yang Mingjie Yao Ying Yan Yanna Liu Xiajie Wen Xiangmei Chen Fengmin Lu |
| author_sort | Danli Yang |
| collection | DOAJ |
| description | 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 (<i>r</i> = 0.540, <i>p</i> < 0.001), higher than that in non-cirrhotic CLD (<i>r</i> = 0.318, <i>p</i> < 0.001) and HCC (<i>r</i> = 0.353, <i>p</i> < 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. |
| first_indexed | 2024-03-09T06:06:34Z |
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| language | English |
| last_indexed | 2024-03-09T06:06:34Z |
| publishDate | 2021-02-01 |
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| series | Biomolecules |
| spelling | doaj.art-ad9e20a36a704f48bc37b9c839ef329b2023-12-03T12:03:11ZengMDPI AGBiomolecules2218-273X2021-02-0111220510.3390/biom11020205Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver DiseaseDanli Yang0Mingjie Yao1Ying Yan2Yanna Liu3Xiajie Wen4Xiangmei Chen5Fengmin Lu6Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, ChinaGolgi 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 (<i>r</i> = 0.540, <i>p</i> < 0.001), higher than that in non-cirrhotic CLD (<i>r</i> = 0.318, <i>p</i> < 0.001) and HCC (<i>r</i> = 0.353, <i>p</i> < 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.https://www.mdpi.com/2218-273X/11/2/205liver diseasebile acidsGolgi protein 73deoxycholic acidnuclear factor-kappa B |
| spellingShingle | Danli Yang Mingjie Yao Ying Yan Yanna Liu Xiajie Wen Xiangmei Chen Fengmin Lu Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease Biomolecules liver disease bile acids Golgi protein 73 deoxycholic acid nuclear factor-kappa B |
| title | Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease |
| title_full | Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease |
| title_fullStr | Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease |
| title_full_unstemmed | Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease |
| title_short | Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease |
| title_sort | deoxycholic acid upregulates serum golgi protein 73 through activating nf κb pathway and destroying golgi structure in liver disease |
| topic | liver disease bile acids Golgi protein 73 deoxycholic acid nuclear factor-kappa B |
| url | https://www.mdpi.com/2218-273X/11/2/205 |
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