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

• Main Authors: Carmen De Miguel, Abigayle C. Kraus, Mitchell A. Saludes, Prasad Konkalmatt, Almudena Ruiz Domínguez, Laureano D. Asico, Patricia S. Latham, Daniel Offen, Pedro A. Jose, Santiago Cuevas
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: International Journal of Molecular Sciences
• Subjects: renal disease; DJ-1; ND-13; renal inflammation; oxidative stress; UUO
• Online Access: https://www.mdpi.com/1422-0067/21/19/7048
• ISSN: 1661-6596; 1422-0067

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 <i>DJ-1^−/−</i> mice underwent UUO and were treated with ND-13 or vehicle for 14 days. ND-13 attenuated the renal expression of fibrotic markers <i>TGF-β</i> and <i>collagen1a1</i> (<i>Col1a1</i>) and inflammatory markers <i>TNF-α</i> and <i>IL-6</i> in C57Bl/6 mice. <i>DJ-1^−/−</i> mice treated with ND-13 presented similar decreased expression of <i>TNF-α</i>, <i>IL-6</i> and <i>TGF-β</i>. However, in contrast to C57Bl/6 mice, ND-13 failed to prevent renal fibrosis or to ameliorate the expression of <i>Col1a1</i> in this genotype. Further, UUO led to elevated urinary levels of the proximal tubular injury marker <i>neutrophil gelatinase-associated lipocalin</i> (NGAL) in <i>DJ-1^−/−</i> 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.