Medical Sciences Graduate Program , Federal University Fluminense (UFF) , Niterói , RJ 24220-900 , Brazil.
Cardiovascular Sciences Graduate Program , Federal University Fluminense (UFF) , Niterói , RJ 24220-900 , Brazil.
Biochemistry. 2019 Apr 16;58(15):2054-2060. doi: 10.1021/acs.biochem.8b01305. Epub 2019 Apr 3.
Recent studies have suggested that uremic toxins such as indoxyl sulfate (IS) and indole-3-acetic acid (IAA) from the metabolism of the gut microbiota may be involved in the inflammatory signaling pathway in chronic kidney disease (CKD) patients through the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The objective of this study was to investigate the possible relationship between uremic toxins (IS and IAA) and AhR protein expression in CKD patients. A cross-sectional observational study involving 17 hemodialysis (HD) [11 men, 55.5 ± 11.7 years of age, 54.0 (25.5-136.0) months of HD, body mass index (BMI) of 25.8 ± 3.8 kg/m] and 15 non-dialysis-dependent (NDD) CKD (8 men, 54.1 ± 18.2 years of age, glomerular filtration rate of 34.8 ± 21.0 mL/min/1.73 m, BMI of 27.4 ± 5.0 kg/m) patients was conducted. IS and IAA levels were measured by reversed-phase high-performance liquid chromatography, and the protein expression levels of AhR and nuclear factor κ B (NF-κB) were evaluated by a Western blot assay. There was no difference in the expression of either AhR or NF-κB in the patients, and as expected, uremic toxin levels were higher in HD patients than in NDD patients. In the overall analysis, AhR protein expression was positively associated with IAA plasma levels ( r = 0.4; p = 0.03) and NF-κB protein expression ( r = 0.62; p = 0.001). Although the role of AhR in inflammation and CVD in CKD patients is far from being completely understood, the association between IAA and AhR observed in this study suggests a possible role for uremic toxins in the cell signaling pathway involved in inflammation in CKD patients.
最近的研究表明，肠道微生物代谢产生的尿毒症毒素，如硫酸吲哚酚（IS）和吲哚-3-乙酸（IAA），可能通过激活芳烃受体（AhR），一种配体激活的转录因子，参与慢性肾脏病（CKD）患者的炎症信号通路。本研究旨在探讨尿毒症毒素（IS 和 IAA）与 CKD 患者 AhR 蛋白表达之间的可能关系。本研究为横断面观察性研究，纳入 17 名血液透析（HD）患者[11 名男性，55.5±11.7 岁，HD 治疗时间 54.0（25.5-136.0）个月，体重指数（BMI）25.8±3.8kg/m2]和 15 名非透析依赖性（NDD）CKD 患者[8 名男性，54.1±18.2 岁，肾小球滤过率 34.8±21.0mL/min/1.73m2，BMI 27.4±5.0kg/m2]。采用反相高效液相色谱法测定 IS 和 IAA 水平，Western blot 法测定 AhR 和核因子κB（NF-κB）的蛋白表达水平。患者的 AhR 和 NF-κB 表达无差异，且尿毒症毒素水平在 HD 患者中高于 NDD 患者，与预期结果一致。在总体分析中，AhR 蛋白表达与 IAA 血浆水平呈正相关（r=0.4；p=0.03），与 NF-κB 蛋白表达呈正相关（r=0.62；p=0.001）。虽然 AhR 在 CKD 患者炎症和心血管疾病中的作用远未完全阐明，但本研究观察到的 IAA 与 AhR 之间的关联表明，尿毒症毒素可能在 CKD 患者炎症相关的细胞信号通路中发挥作用。
