Peres Rodrigo A S, Silva-Aguiar Rodrigo P, Teixeira Douglas E, Peruchetti Diogo B, Alves Sarah A S, Leal Anna Beatriz C, Castro Guilherme F, Ribeiro Natalia B S, Guimarães Fernanda V, Pinheiro Ana Acacia S, Silva Patrícia M R E, Martins Marco A, Caruso-Neves Celso
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Biochim Biophys Acta Gen Subj. 2023 Apr;1867(4):130314. doi: 10.1016/j.bbagen.2023.130314. Epub 2023 Jan 21.
Subclinical acute kidney injury (subAKI) is characterized by tubule-interstitial injury without significant changes in glomerular function. SubAKI is associated with the pathogenesis and progression of acute and chronic kidney diseases. Currently, therapeutic strategies to treat subAKI are limited. The use of gold nanoparticles (AuNPs) has shown promising benefits in different models of diseases. However, their possible effects on subAKI are still unknown. Here, we investigated the effects of AuNPs on a mouse model of subAKI. Animals with subAKI showed increased functional and histopathologic markers of tubular injury. There were no changes in glomerular function and structure. The animals with subAKI also presented an inflammatory profile demonstrated by activation of Th1 and Th17 cells in the renal cortex. This phenotype was associated with decreased megalin-mediated albumin endocytosis and expression of proximal tubular megalin. AuNP treatment prevented tubule-interstitial injury induced by subAKI. This effect was associated with a shift to an anti-inflammatory Th2 response. Furthermore, AuNP treatment preserved megalin-mediated albumin endocytosis in vivo and in vitro. AuNPs were not nephrotoxic in healthy mice. These results suggest that AuNPs have a protective effect in the tubule-interstitial injury observed in subAKI, highlighting a promising strategy as a future antiproteinuric treatment.
亚临床急性肾损伤（subAKI）的特征是肾小管间质损伤，而肾小球功能无明显变化。SubAKI与急性和慢性肾脏疾病的发病机制及进展相关。目前，治疗subAKI的策略有限。金纳米颗粒（AuNPs）在不同疾病模型中已显示出有前景的益处。然而，它们对subAKI的可能影响仍不清楚。在此，我们研究了AuNPs对subAKI小鼠模型的影响。患有subAKI的动物显示出肾小管损伤的功能和组织病理学标志物增加。肾小球功能和结构无变化。患有subAKI的动物在肾皮质中也表现出由Th1和Th17细胞激活所证明的炎症特征。这种表型与巨膜蛋白介导的白蛋白内吞作用降低及近端肾小管巨膜蛋白表达减少有关。AuNP治疗可预防subAKI诱导的肾小管间质损伤。这种作用与向抗炎性Th2反应的转变有关。此外，AuNP治疗在体内和体外均保留了巨膜蛋白介导的白蛋白内吞作用。AuNPs对健康小鼠无肾毒性。这些结果表明，AuNPs对subAKI中观察到的肾小管间质损伤具有保护作用，突出了其作为未来抗蛋白尿治疗的一种有前景的策略。
