ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction
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...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7048 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Carmen De Miguel |
| collection | DOAJ |
| description | 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<sup>−/−</sup></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<sup>−/−</sup></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 neutrophil gelatinase-associated lipocalin (NGAL) in <i>DJ-1<sup>−/−</sup></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. |
| first_indexed | 2024-03-10T16:04:55Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:04:55Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a7dd094e8d05432c963853a2a34f152d2023-11-20T15:01:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119704810.3390/ijms21197048ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter ObstructionCarmen De Miguel0Abigayle C. Kraus1Mitchell A. Saludes2Prasad Konkalmatt3Almudena Ruiz Domínguez4Laureano D. Asico5Patricia S. Latham6Daniel Offen7Pedro A. Jose8Santiago Cuevas9Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, AL 35233, USASection of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, AL 35233, USADepartment of Medicine, Division of Renal Diseases & Hypertension and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USADepartment of Medicine, Division of Renal Diseases & Hypertension and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USAMolecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB), University Clinical Hospital Virgen Arrixaca, 30120 Murcia, SpainDepartment of Medicine, Division of Renal Diseases & Hypertension and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USAPathology and Internal Medicine The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USANeuroscience Laboratory, The Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, IsraelDepartment of Medicine, Division of Renal Diseases & Hypertension and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USAMolecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB), University Clinical Hospital Virgen Arrixaca, 30120 Murcia, SpainDJ-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<sup>−/−</sup></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<sup>−/−</sup></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 neutrophil gelatinase-associated lipocalin (NGAL) in <i>DJ-1<sup>−/−</sup></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.https://www.mdpi.com/1422-0067/21/19/7048renal diseaseDJ-1ND-13renal inflammationoxidative stressUUO |
| spellingShingle | 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 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 renal disease DJ-1 ND-13 renal inflammation oxidative stress UUO |
| title | ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction |
| title_full | ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction |
| title_fullStr | ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction |
| title_full_unstemmed | ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction |
| title_short | ND-13, a DJ-1-Derived Peptide, Attenuates the Renal Expression of Fibrotic and Inflammatory Markers Associated with Unilateral Ureter Obstruction |
| title_sort | nd 13 a dj 1 derived peptide attenuates the renal expression of fibrotic and inflammatory markers associated with unilateral ureter obstruction |
| topic | renal disease DJ-1 ND-13 renal inflammation oxidative stress UUO |
| url | https://www.mdpi.com/1422-0067/21/19/7048 |
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