ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction.
ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction.
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DOI：
10.3390/ijms21197048
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发表时间：
2020-09-24
影响因子：
5.6
通讯作者：
Cuevas S
中科院分区：
文献类型：
--
作者：
De Miguel C;Kraus AC;Saludes MA;Konkalmatt P;Ruiz Domínguez A;Asico LD;Latham PS;Offen D;Jose PA;Cuevas S
DJ-1是一种氧化还原敏感的伴侣蛋白，据报道在肾脏中具有抗氧化和抗炎特性。20个氨基酸（aa）肽ND-13由来自DJ-1序列的13个高度保守的aa和帮助细胞穿透的TAT衍生的7个aa序列组成。本研究旨在确定ND-13治疗是否可预防与单侧输尿管梗阻（UUO）相关的肾损伤和炎症。雄性C57 Bl/6和DJ-1−/−小鼠接受UUO，并用ND-13或溶剂处理14天。ND-13减弱C57 Bl/6小鼠中纤维化标志物TGF-β和胶原1a 1（Col 1a 1）以及炎症标志物TNF-α和IL-6的肾表达。用ND-13处理的DJ-1−/−小鼠表现出类似的TNF-α、IL-6和TGF-β表达降低。然而，与C57 B1/6小鼠相比，ND-13未能预防肾纤维化或改善该基因型中Col 1a 1的表达。此外，UUO导致DJ-1−/−小鼠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）的尿液水平升高，ND-13使其钝化。我们的研究结果表明，ND-13保护UUO诱导的肾损伤，炎症和纤维化。这些都是肾损伤发病机制中的关键机制。因此，ND-13可能成为预防肾脏疾病的一种新的治疗方法。
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 DJ-1−/− mice underwent UUO and were treated with ND-13 or vehicle for 14 days. ND-13 attenuated the renal expression of fibrotic markers TGF-β and collagen1a1 (Col1a1) and inflammatory markers TNF-α and IL-6 in C57Bl/6 mice. DJ-1−/− mice treated with ND-13 presented similar decreased expression of TNF-α, IL-6 and TGF-β. However, in contrast to C57Bl/6 mice, ND-13 failed to prevent renal fibrosis or to ameliorate the expression of Col1a1 in this genotype. Further, UUO led to elevated urinary levels of the proximal tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL) in DJ-1−/− 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.
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影响因子：
3.7
作者：
Lev N;Barhum Y;Lotan I;Steiner I;Offen D
通讯作者：
Offen D
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
16.6
作者：
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通讯作者：
Yamamoto M
影响因子：
3.7
作者：
Lev N;Barhum Y;Ben-Zur T;Aharony I;Trifonov L;Regev N;Melamed E;Gruzman A;Offen D
通讯作者：
Offen D
影响因子：
19.6
作者：
Lee, Soo Bong;Kalluri, Raghu
通讯作者：
Kalluri, Raghu