Kidney Week

Abstract: SA-PO117

Marked Improvement of Renal Lesions by Treatment with Mimetic Peptide of SOCS1 in the Diabetic Model BTBR ob/ob

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Opazo-Ríos, Lucas, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Lucas Opazo-Ríos,

• Sanchez, Yenniffer, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Yenniffer Sanchez,

• Rodrigues díez, Raúl R., IIS-Fundación Jiménez Díaz-Autónoma University of Madrid, CIBERDEM, Madrid, Spain

Raúl R. Rodrigues díez,

• Carpio, Daniel, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Daniel Carpio,

• Lavoz, Carolina, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Carolina Lavoz,

• Krall, Paola, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Paola Krall,

• Egido, Jesus, IIS-Fundación Jiménez Díaz-Autónoma University of Madrid, CIBERDEM, Madrid, Spain

Jesus Egido,

• Gomez-Guerrero, Carmen, IIS-Fundación Jiménez Díaz-Autónoma University of Madrid, CIBERDEM, Madrid, Spain

Carmen Gomez-Guerrero,

• Droguett, Maria Alejandra, Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Maria Alejandra Droguett,

• Mezzano, Sergio A., Universidad Austral de Chile, Valdivia, Región de los Ríos, Chile

Sergio A. Mezzano,

Group or Team Name

• Unidad de Nefrología, Facultad de Medicina, UACH.

Background

Type 2 Diabetes (T2D) is a global public health problem, with Diabetic Nephropathy (DN) being the main cause of chronic renal disease worldwide. Although current treatments delay the evolution of the disease, it is necessary to establish new therapeutic strategies in early stages of DN, in order to promote renoprotection. The JAK/STAT signaling pathway participates in the diabetic renal disease, through the induction of genes involved in inflammation and oxidative stress. Among the different mechanisms for JAK/STAT control, the family of SOCS proteins has been proposed as new molecular targets for the treatment of DN.
Our aim was to evaluate the effect of SOCS1 mimetic peptide (MiS1) on the development of early renal damage associated with T2D.

Methods

Four groups of BTBR ob/ob mice (6 weeks old) were treated 3 days/week for 7 weeks with active peptide (2 and 4 μg), mutant peptide (4 µg) or vehicle. At the end of the study, animals were sacrificed to obtain blood, urine and kidney tissue samples for further analysis.

Results

The treatment of diabetic mice with active MiS1 significantly reduced the ACR ratio and renal weight, improves the glomerular and tubulointerstitial damage and increased podocyte numbers. Treated mice exhibited a decrease in the renal inflammatory infiltrate (F4/80 and CD3), lower gene expression of proinflammatory cytokines (Tnfα and Il-12) and chemokines (Ccl2 and Ccl5) and reduced phosphorylation of STAT1 and STAT3. No changes were observed in glycemia and body weight.
Concomitantly, peptide administration diminished the renal levels of superoxide anion and 8-hydroxy-2'-deoxyguanosine (marker of DNA oxidative damage) and altered the expression of the Nrf2/-heme oxygenase-1 pathway and redox balance enzymes (Nox4, Sod1 and Catalase). Finally, we observed a reduction of lipid peroxidation (4-hydroxy-2-hexenal) and gene expression of scavenger receptors (SR-B/CD36 and SR-A/CD204).

Conclusion

In conclusion, the MiS1 peptide improves the renal damage and is efective in modulating the inflammatory milieu and oxidative stress in an early renal damage in the BTBR ob/ob model.

Fondecyt Project N° 1160465. PhD. Grant N° 21150768, CONICYT, CHILE.
MINECO Project SAF2015-63696R and FIS Proyect PI17/01495, SPAIN.

Funding

• Government Support - Non-U.S.