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

International Journal of Molecular Sciences

MitchellA. Saludes¹  LaureanoD. Asico¹  Prasad Konkalmatt¹  PedroA. Jose¹  Santiago Cuevas²  AlmudenaRuiz Domínguez²  Daniel Offen³  PatriciaS. Latham⁴  AbigayleC. Kraus⁵  CarmenDe Miguel⁵ 

[1] 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;Molecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB), University Clinical Hospital Virgen Arrixaca, 30120 Murcia, Spain;Neuroscience Laboratory, The Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel;Pathology and Internal Medicine The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA;Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, AL 35233, USA;

关键词: renal disease;    DJ-1;    ND-13;    renal inflammation;    oxidative stress;    UUO;   

DOI  :  10.3390/ijms21197048

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown