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ND-13,一种 DJ-1 衍生肽,可减轻与单侧输尿管梗阻相关的纤维化和炎症标志物在肾脏中的表达。

ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction.

机构信息

Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, AL 35233, USA.

Department of Medicine, Division of Renal Diseases & Hypertension and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.

出版信息

Int J Mol Sci. 2020 Sep 24;21(19):7048. doi: 10.3390/ijms21197048.

Abstract

DJ-1 is a redox-sensitive chaperone with reported antioxidant and anti-inflammatory properties in the kidney. The 20 amino acid (aa) peptide ND-13 consists of 13 highly conserved aas from the DJ-1 sequence and a TAT-derived 7 aa sequence that helps in cell penetration. This study aimed to determine if ND-13 treatment prevents the renal damage and inflammation associated with unilateral ureter obstruction (UUO). Male C57Bl/6 and mice underwent UUO and were treated with ND-13 or vehicle for 14 days. ND-13 attenuated the renal expression of fibrotic markers and () and inflammatory markers and in C57Bl/6 mice. mice treated with ND-13 presented similar decreased expression of , and . However, in contrast to C57Bl/6 mice, ND-13 failed to prevent renal fibrosis or to ameliorate the expression of in this genotype. Further, UUO led to elevated urinary levels of the proximal tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL) in mice, which were blunted by ND-13. Our results suggest that ND-13 protects against UUO-induced renal injury, inflammation and fibrosis. These are all crucial mechanisms in the pathogenesis of kidney injury. Thus, ND-13 may be a new therapeutic approach to prevent renal diseases.

摘要

DJ-1 是一种氧化还原敏感的伴侣蛋白,据报道具有抗氧化和抗炎特性,在肾脏中发挥作用。由 DJ-1 序列的 13 个高度保守的氨基酸和一个有助于细胞穿透的 TAT 衍生的 7 个氨基酸序列组成的 20 个氨基酸 (aa) 肽 ND-13。本研究旨在确定 ND-13 治疗是否可以预防与单侧输尿管梗阻 (UUO) 相关的肾脏损伤和炎症。雄性 C57Bl/6 和 小鼠接受 UUO 手术,并接受 ND-13 或载体治疗 14 天。ND-13 减轻了 C57Bl/6 小鼠肾脏中纤维化标志物 和 () 和炎症标志物 和 的表达。 小鼠用 ND-13 处理后, 、 和 的表达也类似减少。然而,与 C57Bl/6 小鼠不同,ND-13 未能预防这种基因型的肾脏纤维化或改善 的表达。此外,UUO 导致 小鼠尿中近端肾小管损伤标志物中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 的水平升高,而 ND-13 则减弱了这种升高。我们的结果表明,ND-13 可预防 UUO 诱导的肾脏损伤、炎症和纤维化。这些都是肾脏损伤发病机制中的关键机制。因此,ND-13 可能是预防肾脏疾病的一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df1/7582723/2f09d5cee31a/ijms-21-07048-g001.jpg

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