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利用阻塞性肾病的病理生理改变通过氧化铈纳米颗粒治疗肾纤维化

Leveraging the Pathophysiological Alterations of Obstructive Nephropathy to Treat Renal Fibrosis by Cerium Oxide Nanoparticles.

作者信息

Saifi Mohd Aslam, Peddakkulappagari Chandra Sekhar, Ahmad Altaf, Godugu Chandraiah

机构信息

Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, Telangana, India.

Department of Botany, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.

出版信息

ACS Biomater Sci Eng. 2020 Jun 8;6(6):3563-3573. doi: 10.1021/acsbiomaterials.9b01944. Epub 2020 May 14.

Abstract

Chronic kidney disease (CKD) has wide prevalence globally that affects a considerable population and has renal fibrosis (RF) as a hallmark feature. RF is characterized by abnormal deposition of extracellular matrix (ECM) in the interstitial space of renal tissue. There are only few studies where nanoparticles (NPs) were used for targeting the kidney mainly due to their size-dependent constraints. Further, most of the studies have been carried out in healthy animals. As the diseased kidney becomes susceptible to accumulation of nanoparticles, we hypothesized that nanoparticles (size ∼10 nm) could reach the kidney and might provide protective effects due to their inherent properties. We investigated the protective effects of cerium oxide nanoparticles (CONPs) with promising antioxidant activity in a CKD model. We, to the best of our knowledge, are first to report that CONPs abrogated RF by inhibiting transforming growth factor-β (TGF-β) signaling and epithelial-mesenchymal transition (EMT) in a fibrotic kidney.

摘要

慢性肾脏病(CKD)在全球范围内广泛流行,影响着相当多的人群,其标志性特征是肾纤维化(RF)。RF的特征是细胞外基质(ECM)在肾组织间质空间异常沉积。由于纳米颗粒(NPs)存在尺寸相关的限制,仅有少数研究将其用于靶向肾脏。此外,大多数研究是在健康动物身上进行的。由于患病肾脏容易积累纳米颗粒,我们推测纳米颗粒(尺寸约为10纳米)可以到达肾脏,并且因其固有特性可能提供保护作用。我们在CKD模型中研究了具有良好抗氧化活性的氧化铈纳米颗粒(CONPs)的保护作用。据我们所知,我们首次报道CONPs通过抑制纤维化肾脏中的转化生长因子-β(TGF-β)信号传导和上皮-间质转化(EMT)来消除肾纤维化。

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