The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride-Induced Liver Injury.
The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride-Induced Liver Injury.
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DOI：
10.1016/j.gastha.2022.09.008
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Ghishan, Fayez K
中科院分区：
文献类型：
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作者：
Tong, Huan;Bernardazzi, Claudio;Curiel, Leslie;Xu, Hua;Ghishan, Fayez K
钠-氢交换器8（NHE 8）在组织阵列中表达，并且具有超越简单地跨细胞膜交换钠和氢的多效性功能。本研究探讨了肝脏NHE 8的表达模式及其在四氯化碳（CCl 4）诱导的肝损伤中的作用。在不同年龄的小鼠肝脏和HepG 2细胞中研究NHE 8表达模式。将CCl 4给予小鼠以测定NHE 8在CCl 4诱导的肝损伤中的表达。用肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β处理HepG 2细胞，观察其对NHE 8表达的影响。还在NHE 8 KO小鼠中使用CCl 4诱导的急性和慢性肝损伤，以确定NHE 8缺乏在肝损伤中的作用。NHE 8主要在小鼠肝细胞和HepG 2细胞中的肝细胞的外周区域中检测到。肝脏NHE 8表达量为NHE 1的47%，在哺乳期最低，4周龄时达到平台期。与葡聚糖硫酸钠结肠炎减少肠道NHE 8类似，CCl 4诱导的急性肝损伤也抑制NHE 8表达。肝脏中不存在NHE 8显示出异常的肝细胞形态，并且具有升高的IL-1β和Lgr 5表达。然而，与NHE 8缺乏增强葡聚糖硫酸钠诱导的结肠组织损伤不同，肝脏中NHE 8的缺乏不会加剧CCl 4诱导的肝损伤。尽管在CCl 4诱导的肝损伤中TNF-α和IL-1β均升高，但它们不能抑制肝细胞中NHE 8的表达，这与TNF-α介导的肠中NHE 8的抑制相反。肝脏NHE 8具有不同于肠道的独特作用。
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. 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. 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. Liver NHE8 has unique roles that are different from the intestine.