Advanced Oxidation Protein Products Activate Intrarenal Renin-Angiotensin System via a CD36-Mediated, Redox-Dependent Pathway
Advanced Oxidation Protein Products Activate Intrarenal Renin-Angiotensin System via a CD36-Mediated, Redox-Dependent Pathway
复制标题
高级氧化蛋白产品通过 CD36 介导的氧化还原依赖性途径激活肾内肾素-血管紧张素系统。
DOI：
10.1089/ars.2012.4603
复制
发表时间：
2013-01-01
影响因子：
6.6
通讯作者：
Nie, Jing
中科院分区：
文献类型：
--
作者：
Cao, Wei;Xu, Jie;Nie, Jing
目标
肾内肾素-血管紧张素系统(RAS)的激活对慢性肾脏疾病(CKDS)的进展有不利影响，但肾内RAS的调节尚不清楚。本研究的目的是评价高级氧化蛋白产物(AOPPs)在肾内RAS激活中的作用。
结果
AOPPs可上调培养的近端肾小管上皮细胞RAS的几乎所有组分的表达，并增强血管紧张素转换酶的活性。AOPP-白蛋白的触发作用是未修饰白蛋白的100倍。AOPP-白蛋白的作用主要由CD36依赖的氧化还原敏感信号介导，涉及蛋白激酶Cα、NADPH氧化酶和核因子-κB/激活蛋白-1的激活。单侧肾切除大鼠慢性AOPP-白蛋白负荷导致AOPP在肾小管上皮细胞沉积，并伴有局部RAS激活和功能紊乱，如尿白蛋白排泄增加。19例IgA肾病患者肾活检组织中血管紧张素Ⅱ的表达与人肾小管上皮细胞中AOPPs的积聚有关。
创新与总结
这项研究首次证明了AOPPs修饰的白蛋白通过CD36介导的氧化还原依赖的途径作为肾内RAS的强大触发器发挥作用。鉴于AOPPs积聚在糖尿病和CKD中普遍存在的事实，靶向AOPPs可能成为CKD治疗干预的一种策略。抗氧化剂。氧化还原信号。18，19-35。
AIMS
Activation of intrarenal renin-angiotensin system (RAS) has a detrimental effect on the progression of chronic kidney diseases (CKDs), although the regulation of intrarenal RAS remains unclear. The aim of the present study was to evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal RAS activation.
RESULTS
AOPPs upregulated the expression of almost all components of RAS and increased activity of angiotensin-converting enzyme in cultured proximal tubular epithelial cells. The triggering effect of AOPP-albumin was 100-times stronger than that of unmodified albumin. The effect of AOPP-albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling involving activation of protein kinase Cα, NADPH oxidase, and nuclear factor-κB/activation protein-1. Chronic AOPP-albumin loading in unilateral nephrectomy rats resulted in deposition of AOPPs in renal tubular cells accompanied with local RAS activation and functional perturbations such as increase in urinary albumin excretion. Accumulation of AOPPs was also detected in human renal tubular cells and correlated with expression of angiotensin II in renal biopsies from 19 patients with IgA nephropathy.
INNOVATION AND CONCLUSION
This study demonstrated for the first time that AOPPs modified albumin functions as a strong trigger of intrarenal RAS via a CD36-mediated, redox-dependent pathway. Given the fact that accumulation of AOPPs is prevalent in diabetes and CKD, targeting AOPPs could be a strategy for the therapeutic intervention of CKD. Antioxid. Redox Signal. 18, 19-35.