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

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 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.

PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress

“…In vivo, Park7 deficiency aggravated UUO-induced renal fibrosis, as manifested by more severe tubular atrophy and kidney deposition of extracellular matrix proteins in Park7 ko mice than in WT mice following UUO (Figure 2). Consistently, the latest work by Miguel et al demonstrated the inhibitory effect of ND-13 (PARK7 peptide) on UUO-induced renal fibrosis (36). Collectively, these studies indicate that renal tubular cell PARK7 has an anti-fibrotic, protective function in kidney diseases.…”

“…ND-13 is PARK7-based peptide that has been shown be cytoprotective under stressful conditions, such as Cerebral reperfusion injury (32). Miguel et al showed that UUO mice received ND-13 (3 mg/kg of body weight) via subcutaneous injection starting from the day of surgery, daily for 14 days showed reduced expression of fibrotic and inflammatory markers compared to UUO mice received vehicle, suggesting a beneficial effect of ND-13 in renal fibrosis (36). In the present study, administration of ND-13 (2 mg/kg of body weight) via tail veil injection starting from the day after surgery, daily for 7 days reduced the renal levels of Tgfb mRNA, Tnfa mRNA and infiltration of macrophages into kidney tissues (Figures 8G-J).…”

DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion

“…To examine whether DJ-1 affects microglial/macrophage polarization and participates in the inflammatory response, we used ND13 (DJ-1 based peptide) ( Glat et al, 2016 ; Molcho et al, 2018 ; Miguel et al, 2020 ) and DJ-1 siRNA to produce an effect on DJ-1 expression. Then, we measured the expression of microglial cell marker proteins (pro-inflammatory markers: iNOS and CD86; anti-inflammatory markers: Arg1 and CD163) and the expression of inflammatory mediators by Western blotting.…”

“…ND13 is a newly discovered polypeptide that consists of 13 DJ-1-derived amino acids and 7 TAT-derived amino acids ( Glat et al, 2016 ; Molcho et al, 2018 ; Miguel et al, 2020 ). ND13 has been reported to alleviate dopaminergic system dysfunction in a Parkinson’s disease model ( Longa et al, 1989 ).…”

“…ND13 has been reported to alleviate dopaminergic system dysfunction in a Parkinson’s disease model ( Longa et al, 1989 ). ND13 significantly improved motor function in mice in a stroke model ( Molcho et al, 2018 ), protected cells from oxidative stress, improved survival, and exerted a neuroprotective effect against SIN-1-induced neurotoxicity ( Miguel et al, 2020 ). However, whether ND13 has a similar effect in cerebral I/R model has not been reported.…”