Abstract: FR-PO348

Adiponectin Attenuates Kidney Injury and Fibrosis in Deoxycorticosterone Acetate-Salt and Angiotensin II Induced CKD Mice

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Tian, Mi, University of Utah Health, Salt Lake City, Utah, United States
  • Tang, Li, University of Utah Health, Salt Lake City, Utah, United States
  • Beddhu, Srini, University of Utah Health, Salt Lake City, Utah, United States
  • Huang, Yufeng, University of Utah Health, Salt Lake City, Utah, United States
Background

Adiponectin (ApN) is a multifunctional adipokine with insulin-sensitizing, anti-inflammatory, and vasoprotective properties. However high, rather than low, concentrations of ApN are unexpectedly found in patients with chronic kidney disease (CKD) via an as yet unknown mechanism and the role of ApN in CKD is unclear. We, herein, investigated the effect of ApN overexpression on the progression of renal injury resulted from deoxycorticosterone acetate-salt (DOCA) and angiotensin II (DOCA+AII) infusion using a transgenic, inducible, hepatic ApN-overexpressing mouse model.

Methods

Uninephrectomy was firstly performed on all experimental mice. Two weeks after uninephrectomy, three groups of male mice (wild type receiving no infusion and normal drinking water (WT), wild type and cyp1a1 ApN transgenic mice receiving DOCA+AII infusion (WT/DOCA+AII and ApN-Tg/DOCA+AII) and 1% NaCl in drinking water) (n=5/each group) were then assigned to receive a normal diet containing 0.15% of the transgene inducer indol-3-carbinol (I3C) for 3 weeks.

Results

The I3C-induced ApN-Tg/DOCA+AII mice, not the WT or WT/DOCA+AII mice, overexpressing ApN in liver resulted in 3.15-fold increases in circulating ApN levels than non-transgenic controls. Of note, these transgenic mice receiving DOCA+AII infusion were still hypertensive (SBP, 148±5.09 vs. 148.07±3.43 mmHg, P>0.05 vs. WT/DOCA+AII) but had much less albuminuria and glomerular and tubulointerstitial fibrosis (decreased by 67.3%, 76.6% and 67.3% respectively (P<0.001), when compared to WT/DOCA+AII), which were associated with reduced podocyte injury determined by ameliorated DOCA+AII-induced podocyte loss and foot process effacement; and alleviated tubular injury determined by ameliorated DOCA+AII-induced increases in renal KIM-1 and NGLA mRNA expression and decreases in renal cubilin and megalin mRNA expression. In addition, renal macrophage infiltration and productions of NF-kB-p65, Nox2 and p47phox, markers of inflammation and oxidative stress, which were induced by DOCA+AII infusion in WT mice, were markedly reduced in ApN-Tg mice.

Conclusion

These results indicate that elevated ApN in CKD mouse model is renal protective. Enhancing adiponectin production or signaling may have therapeutic potential for renal disease.