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Kidney Week

Abstract: PO0607

The Macrophage Recruitment in the Unilateral Ureteral Obstruction Is Associated with the Raise of MCP-1 and Is Dependent of Lipocalin 2 Expression

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Figueroa, Stefanny M., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile
  • Lozano, Mauricio A., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile
  • Lobos, Carolina A., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile
  • Reyes Osorio, Javier Ignacio, Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile
  • Araos, Patricio A., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile
  • Amador, Cristián A., Universidad Autonoma de Chile - Campus El Llano Subercaseaux, Santiago, Chile

Group or Team Name

  • Laboratory of Renal Physiopathology
Background

The persistent renal inflammation has been proposed as a crucial mechanism at the early stages of renal disease. The macrophages recruitment, as part of the pathogenic events, depends of the monocyte chemoattractant protein-1 (MCP-1) raise. In addition, studies in patients have demonstrated that neutrophil gelatinase-associated lipocalin (NGAL, also called Lipocalin-2), it is overexpressed during early stages of renal lesion. However, whether NGAL is relevant for macrophages recruitment at renal level, and if this is related to the increase of MCP-1, remains unknown. Our objective was to determine whether NGAL promotes the pro-inflammatory status during the unilateral ureteral obstruction (UUO), characterized by the macrophage recruitment and the increase of MCP-1.

Methods

Male C57BL/6 Wild type (WT) y NGAL-KO mice (8-12 weeks) were underwent to UUO and to Sham surgery (control group) during 3 and 7 days (n=8), in order to determine the associated damage at kidney level and the raise of MCP-1 in peripheral blood mononuclear cells (PBMC).

Results

In WT mice, the UUO induced luminal tubular dilation starting at 3 days (P<0.001 vs. Sham), and an induction of plasma urea (76.36 ± 5.37 mg/dL. P<0.01 vs. Sham). In addition, UUO increased NGAL levels in PBMC, plasma and urine (24.1 μg/L in Sham vs. 103.8 μg/L and 134.5 μg/L in UUO, at 3 and 7 days, respectively). This was in accordance with the renal induction of NGAL (mRNA and protein, P<0.001 vs. Sham), and with the increase of mRNA for the following pro-inflammatory mediators: TGF-β1, CCL5 (RANTES) and MCP-1, with a peak at 7-days. The genetic abalation of NGAL prevented tubular dilation (34.24 ± 6.55 μm. P<0.01 vs. UUO WT) and the rise of MCP-1 induced by UUO in kidney and PBMC (P<0.001 vs. WT). This was accompanied with a low grade of macrophage infiltration in kidney of NGAL-KO mice underwent to UUO (15.2% in WT vs. 7.3% in NGAL-KO).

Conclusion

The renal overexpression of MCP-1 and the macrophage recruitment induced by UUO is dependent of NGAL presence. Our results suggest that NGAL, by a regulation on MCP-1, may be crucial for macrophage chemoattraction during the early stages of renal disease.
Acknowledgments. Fondecyt #1201251 and Fondecyt #3201016