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The expression of NHE8 in liver and its role in carbon tetrachloride induced liver injury

Open AccessPublished:September 21, 2022DOI:https://doi.org/10.1016/j.gastha.2022.09.008
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      Abstract

      Background and Aims

      Sodium-hydrogen exchanger 8 (NHE8) is expressed in array of tissues and has pleotropic 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. TNFα and IL1β were used to treat HepG2 cells to evaluate their effect on NHE8 expression. The CCl4-induced acute and chronic liver injury were also used in NHE8KO mice to determine the role 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% ofNHE1, and liver NHE8 expression was the lowest at suckling age and reached plateau at 4weeks of age. Like DSS-colitis reduced intestine 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 IL1β and Lgr5. However, unlike NHE8 deficiency enhance DSS-induced colon tissue damage, the absence of NHE8 in the liver did not exacerbate CCl4-induced liver injury. Although both TNFα and IL1β were elevated in CCl4-induced liver injury, they could not inhibit NHE8 expression in hepatocytes, which is in contrast with TNFα-mediated NHE8 inhibition in the intestine.

      Conclusion

      Liver NHE8 has unique roles that are different from the intestine.

      Key words

      Abbreviations:

      ALT (alanine aminotransferase), AST (aspartate aminotransferase), BW (body weight), CCl4 (carbon tetrachloride), H&E (hematoxylin-eosin), NHE (sodium-hydrogen exchanger), WT (wild-type), KO (knockout), SE (standard error)