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首页> 外文期刊>Life sciences >Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells
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Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells

机译：硫酸吲哚酚通过ROS的产生以及近端小管细胞中NF-κB和p53的激活来上调ICAM-1的肾脏表达

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Aims Intercellular adhesion molecule 1 (ICAM-1) plays an important role in adhesion of monocytes/macrophages to injured tubulointerstitial tissue. The present study aimed to determine if indoxyl sulfate, a uremic toxin, regulates renal expression of ICAM-1. Main methods The effect of indoxyl sulfate on expression of ICAM-1 was determined using human proximal tubular cells (HK-2 cells) and the following animals: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN + IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH + IS). Key findings DN + IS, DH, and DH + IS rats showed significantly increased mRNA expression of ICAM-1 in the kidneys compared with DN rats. DH + IS rats showed significantly increased mRNA expression of ICAM-1 in the kidneys compared with DH rats. Immunohistochemistry revealed that ICAM-1 was localized in the cytoplasm of renal tubular cells, and was most prominently expressed in DH + IS rats. Indoxyl sulfate upregulated mRNA and protein expression of ICAM-1 in HK-2 cells. Inhibitors of NADPH oxidase (diphenylene iodonium chloride), NF-κB (isohelenin) and p53 (pifithrin-α,p-nitro) suppressed indoxyl sulfate-induced expression of ICAM-1 mRNA and protein in HK-2 cells. Significance Indoxyl sulfate upregulated renal expression of ICAM-1 through production of reactive oxygen species (ROS) such as superoxide, and activation of NF-κB and p53 in proximal tubular cells. Further, administration of indoxyl sulfate promoted ICAM-1 expression in rat kidneys. Thus, accumulation of indoxyl sulfate in chronic kidney disease might be involved in the pathogenesis of tubulointerstitial injury through induction of ICAM-1 in the kidney.
机译：目的细胞间粘附分子1（ICAM-1）在单核细胞/巨噬细胞与受损的肾小管间质组织的粘附中起重要作用。本研究旨在确定硫酸吲哚酚（尿毒症毒素）是否调节ICAM-1的肾脏表达。主要方法使用人类近端肾小管细胞（HK-2细胞）和以下动物确定硫酸吲哚酚对ICAM-1表达的影响：（1）耐Dahl盐的血压正常的大鼠（DN），（2）Dahl盐- （3）达尔盐敏感性高血压硫酸吲哚酚大鼠（DN + IS），（3）达尔盐敏感性高血压硫酸吲哚酚大鼠（DN + IS）。关键发现DN + IS，DH和DH + IS大鼠与DN大鼠相比，肾脏中ICAM-1的mRNA表达显着增加。与DH大鼠相比，DH + IS大鼠肾脏中ICAM-1的mRNA表达显着增加。免疫组织化学显示ICAM-1位于肾小管细胞的细胞质中，并在DH + IS大鼠中最明显地表达。硫酸吲哚酚上调HK-2细胞ICAM-1的mRNA和蛋白表达。 NADPH氧化酶（氯化二亚苯基碘鎓），NF-κB（异海洛因）和p53（菲菲林-α，对硝基）的抑制剂抑制了硫酸吲哚酚诱导的HK-2细胞ICAM-1 mRNA和蛋白的表达。意义硫酸吲哚酚通过产生活性氧（ROS）（如超氧化物）以及激活近端肾小管细胞中的NF-κB和p53来上调ICAM-1的肾脏表达。此外，硫酸吲哚酚的施用促进了大鼠肾脏中ICAM-1的表达。因此，在慢性肾脏疾病中硫酸吲哚酚的积累可能通过在肾脏中诱导ICAM-1而参与了肾小管间质损伤的发病机制。

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