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The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury
BACKGROUND AND AIMS: Sodium-hydrogen exchanger 8 (NHE8) is expressed in array of tissues and has pleiotropic functions beyond simply exchanging sodium and hydrogen across cell membrane. This study investigates the expression pattern of liver NHE8 and its roles in carbon tetrachloride (CCl4)-induced...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019310/ https://www.ncbi.nlm.nih.gov/pubmed/36936401 http://dx.doi.org/10.1016/j.gastha.2022.09.008 |
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author | Tong, Huan Bernardazzi, Claudio Curiel, Leslie Xu, Hua Ghishan, Fayez K. |
author_facet | Tong, Huan Bernardazzi, Claudio Curiel, Leslie Xu, Hua Ghishan, Fayez K. |
author_sort | Tong, Huan |
collection | PubMed |
description | BACKGROUND AND AIMS: Sodium-hydrogen exchanger 8 (NHE8) is expressed in array of tissues and has pleiotropic functions beyond simply exchanging sodium and hydrogen across cell membrane. This study investigates the expression pattern of liver NHE8 and its roles in carbon tetrachloride (CCl4)-induced liver injury. METHODS: NHE8 expression pattern was investigated in mouse livers of different ages and in HepG2 cells. CCl4 was given to mice to determine NHE8 expression in CCl4-induced liver injury. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were used to treat HepG2 cells to evaluate their effect on NHE8 expression. The CCl4-induced acute and chronic liver injuries were also used in NHE8KO mice to determine the role of NHE8 deficiency in liver injury. RESULTS: NHE8 was mainly detected in the peripheral area of hepatocytes in mouse liver and in HepG2 cells. The liver NHE8 expression was 47% of NHE1, and liver NHE8 expression was the lowest at suckling age and reached plateau at 4 weeks of age. Similar to dextran sulfate sodium colitis reduced intestinal NHE8, CCl4-induced acute liver injury also inhibited NHE8 expression. The absence of NHE8 in the liver displayed abnormal hepatocyte morphology and has elevated expression of IL-1β and Lgr5. However, unlike NHE8 deficiency enhanced dextran sulfate sodium-induced colon tissue damage, the absence of NHE8 in the liver did not exacerbate CCl4-induced liver injury. Although both TNF-α and IL-1β were elevated in CCl4-induced liver injury, they could not inhibit NHE8 expression in hepatocytes, which is in contrast with TNF-α–mediated NHE8 inhibition in the intestine. CONCLUSION: Liver NHE8 has unique roles that are different from the intestine. |
format | Online Article Text |
id | pubmed-10019310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-100193102023-03-16 The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury Tong, Huan Bernardazzi, Claudio Curiel, Leslie Xu, Hua Ghishan, Fayez K. Gastro Hep Adv Article BACKGROUND AND AIMS: Sodium-hydrogen exchanger 8 (NHE8) is expressed in array of tissues and has pleiotropic functions beyond simply exchanging sodium and hydrogen across cell membrane. This study investigates the expression pattern of liver NHE8 and its roles in carbon tetrachloride (CCl4)-induced liver injury. METHODS: NHE8 expression pattern was investigated in mouse livers of different ages and in HepG2 cells. CCl4 was given to mice to determine NHE8 expression in CCl4-induced liver injury. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were used to treat HepG2 cells to evaluate their effect on NHE8 expression. The CCl4-induced acute and chronic liver injuries were also used in NHE8KO mice to determine the role of NHE8 deficiency in liver injury. RESULTS: NHE8 was mainly detected in the peripheral area of hepatocytes in mouse liver and in HepG2 cells. The liver NHE8 expression was 47% of NHE1, and liver NHE8 expression was the lowest at suckling age and reached plateau at 4 weeks of age. Similar to dextran sulfate sodium colitis reduced intestinal NHE8, CCl4-induced acute liver injury also inhibited NHE8 expression. The absence of NHE8 in the liver displayed abnormal hepatocyte morphology and has elevated expression of IL-1β and Lgr5. However, unlike NHE8 deficiency enhanced dextran sulfate sodium-induced colon tissue damage, the absence of NHE8 in the liver did not exacerbate CCl4-induced liver injury. Although both TNF-α and IL-1β were elevated in CCl4-induced liver injury, they could not inhibit NHE8 expression in hepatocytes, which is in contrast with TNF-α–mediated NHE8 inhibition in the intestine. CONCLUSION: Liver NHE8 has unique roles that are different from the intestine. 2023 2022-09-22 /pmc/articles/PMC10019310/ /pubmed/36936401 http://dx.doi.org/10.1016/j.gastha.2022.09.008 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Tong, Huan Bernardazzi, Claudio Curiel, Leslie Xu, Hua Ghishan, Fayez K. The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title | The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title_full | The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title_fullStr | The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title_full_unstemmed | The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title_short | The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride–Induced Liver Injury |
title_sort | expression of nhe8 in liver and its role in carbon tetrachloride–induced liver injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019310/ https://www.ncbi.nlm.nih.gov/pubmed/36936401 http://dx.doi.org/10.1016/j.gastha.2022.09.008 |
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