Kidney Week

Abstract: SA-PO1190

The Early Renal Profibrotic Phenotype Caused by 5/6 Nephrectomy in Mice Depends on CD11c+ Antigen-Presenting Cells Population

Session Information

• CKD: Mechanisms - 3
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Reyes Osorio, Javier Ignacio, Universidad San Sebastian Facultad de Medicina y Ciencia, Santiago, Providencia, Chile

Javier Ignacio Reyes Osorio, MSc

• Araos, Patricio A., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, San Miguel, Chile

Patricio A. Araos, PhD

• Figueroa, Stefanny M., Universidad San Sebastian Facultad de Medicina y Ciencia, Santiago, Providencia, Chile

Stefanny M. Figueroa, PhD

• Saez, Javiera, Universidad San Sebastian Facultad de Medicina y Ciencia, Santiago, Providencia, Chile

Javiera Saez, MSc

• Fuenzalida, Maria Jose, Fundacion Ciencia & Vida, Santiago, Huechuraba, Chile

Maria Jose Fuenzalida

• Pacheco, Rodrigo, Fundacion Ciencia & Vida, Santiago, Huechuraba, Chile

Rodrigo Pacheco, PhD

• Amador, Cristián A., Universidad San Sebastian Facultad de Medicina y Ciencia, Santiago, Providencia, Chile

Cristián A. Amador, PhD

Group or Team Name

• Laboratory of Renal Physiopathology.

Background

The recruitment and activation of antigen-presenting cells (APC) represent key mechanisms for the pro-inflammatory stages that lead to fibrosis in the progression of chronic kidney disease (CKD). Our revious experimental studies indicate that dendritic cells-like APC (APC-CD11c⁺) are essential for inflammation, renal dysfunction, and heart fibrosis in mice with hypertensive nephropathy. Although that we have previously demonstrated that APC-CD11c⁺ would not contribute to the inflammatory processes in the experimental unilateral ureteral obstruction, it is still unknown whether these cells contribute to the renal pro-fibrotic status in a model of CKD with reduction of renal function. Our objective was to determine whether the depletion of APC-CD11c⁺ prevents the early renal pro-fibrotic status in a 5/6 nephrectomy model (Nx_5/6).

Methods

Male CD11c.DOG mice (8-12 wo, n=3-7), which can be depleted of APC-CD11c⁺ by using diphtheria toxin (DT), underwent to the Nx_5/6 or Sham surgery (control) for 5-days. These groups received vehicle (Vh) or DT (8ng/g/d, ip) from the beginning of the experiment, where those animals-DT+ with a reduction >60% of APC-CD11c⁺ were selected. Biochemical, histological and molecular analyses were performed.

Results

Nx_5/6 caused a trend increase in plasma creatinine (p=0.16 vs Sham-Vh), and in blood urea nitrogen (p=0.08 vs Sham-Vh). In addition, Nx_5/6 caused a significant increase in renal fibrotic area and was associated with the overexpression in the mRNA for the following pro-fibrotic markers: Collagen (COL)1A1, COL3A1 and Fn-I (p<0.05 vs Sham-Vh), and the pro-inflammatory mediators: Interleukin (IL)-6 and Lipocalin-2 (NGAL). Depletion of APC-CD11c⁺ in Nx_5/6 animals did not alter the plasma parameters analyzed for determining renal function, but it did prevent renal fibrosis (3.79% vs 5.80% Nx_5/6-Vh; p<0.05), and the increase of mRNA for COL3A1 (p<0.05). In addition, the use of DT was associated with a lower abundance of COL1A1 and Fn I (p=0.07 and p=0.12, vs Nx_5/6-Vh, respectively), without affecting any pro-inflammatory mediator.

Conclusion

APC-CD11c⁺ depletion prevents the early renal profibrotic phenotype in the Nx_5/6 model, providing new background related to the importance of APCs in the early progression of CKD.

Funding

• Government Support – Non-U.S.