The Effect of NGAL Receptor in a Model of Unilateral Ureteral Obstruction: A New Role in the Renal Fibrosis Progression?

Introduction: Different studies have proposed that chronic kidney disease (CKD) can progress with high levels of Neutrophil Gelatinase-Associated Lipocalin (NGAL) at renal, plasma and urinary levels. Studies carried out by our group and others indicate that this increase would favor the pro-inflammatory events that promote renal fibrosis. Additionally, it has been suggested that the activation of the NGAL receptor (24p3R), a protein with apical expression at the level of distal nephron, would promote pro-inflammatory and pro-fibrotic pathways. However, the role of 24p3R in the damage processes characteristic of CKD progression remains completely unknown. Objective: To study the effect of 24p3R on renal damage induced by a mouse model of unilateral ureteral obstruction (UUO). Methods: Male 24p3R +/+ and 24p3R +/- mice aged 8–12 weeks (n=6) underwent UUO or Sham surgery (control) for 7 days. We characterized the renal abundance of NGAL and 24p3R by RT-qPCR and immunohistochemistry, respectively. Histological and functional analyses were also performed. All data are presented as mean ± S.E. Results: UUO induced tubular dilatation compared with the Sham group (Sham=12.67±0.24 vs. UUO=27.33±0.49µm; p<0.001), whereas creatinine and blood urea nitrogen levels did not vary significantly between the 24p3R +/+ and 24p3R +/- groups subjected to UUO. Interestingly, 24p3R was identified in the apical membrane of renal tubules by immunohistochemistry, and its expression was more diffuse in heterozygous animals and with ∼20% less abundance compared to 24p3R +/+ . In addition, we observed that UUO was associated with renal fibrosis in 24p3R +/+ animals, which was maintained with a lower intensity in the heterozygous condition. Finally, and by RT-qPCR, we found that in UUO there was a 7.5-fold increase in renal mRNA for NGAL (p<0.001) and 7-fold increase for collagen (COL)1A1 in 24p3R +/+ animals (p<0.001). The latter was prevented in the 24p3R +/- condition and confirmed by Western Blotting studies(p<0.05). Conclusion: A less abundance for the NGAL receptor is associated with a lower development of renal fibrosis induced by UUO, which is consistent with a regulation of COL1A1 renal abundance. These results suggest that apical expression of 24p3R may participate in the fibrosis progression during CKD. Fondecyt #1231909 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.