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Abstract: PO2489

AIM2 Modulates Renal Metabolic Profile and Inflammation in Acute and Chronic Kidney Injury

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Silva, Magaiver Andrade, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Watanabe, Ingrid Kazue Mizuno, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Foresto-Neto, Orestes, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Honda, Tâmisa Seeko, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • da Silva, Ana Ruth Paolinetti Alves, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Cenedeze, Marcos A., Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Pacheco-Silva, Alvaro, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Camara, Niels Olsen Saraiva, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
Background

The absent in melanoma 2 (AIM2) is cytosolic double-stranded DNA receptor expressed in the kidney. AIM2 activation initiates the assembly of the inflammasome, culminating in inflammatory response. Inflammasomes cause metabolic dysregulation and drive pathology in a wide variety of human diseases. So far, the function and how AIM2 affects inflammatory and renal metabolic profile in acute and chronic injury is poorly described.

Methods

The wild-type (WT) and AIM2 KO mice were submitted to cisplatin-induced acute kidney injury or unilateral ureter obstruction (UUO), a chronic kidney disease model. We evaluated renal structure and function, fibrotic molecules, fibronectin (FN) and type I collagen (COL1) and inflammation (IL-1β, IL-6). The expression of carnitine palmitoyltransferase 1 (CPT1a), involved in fatty acid oxidation (the main energy source of kidneys), and glycolytic enzyme expression, pyruvate kinase M2 (PKM2) were used as an indicative of metabolic alteration. The AIM2 activation was also investigated in proximal tubular cells (PTCs).

Results

The severe tissue injury induced in WT mice by cisplatin was markedly attenuated in AIM2 KO mice, evidenced by reduction in tubular dilatation and amelioration of renal function. Moreover, AIM2 deletion impaired the reduction of CPT1a expression. In mice model of UUO, we observed an increase of AIM2 expression, concomitantly with increase of IL-1β, IL-6, FN and COL1. Moreover, the animals presented reduction of CPT1a and increase of PKM2, suggesting a metabolic reprogramming in the kidneys. The AIM2 deficiency attenuated the renal injury, fibrosis, inflammation, and CPT1a levels did not change after kidney injury. In vitro study, the AIM2 activation caused metabolic reprogramming in PTCs, accompanied by increase of proinflammatory and profibrotic markers.

Conclusion

AIM2 activation drives acute e chronic kidney injuries. However, a better understand on how AIM2 affects PTCs metabolism and its connection with inflammation and kidney injury is needed.

Funding

  • Government Support – Non-U.S.