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Kidney Week

Abstract: PO0612

Indoleamine-2, 3-Dioxygenase Activates Wnt/β-Catenin to Induce Kidney Fibrosis

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

  • Pan, Binbin, Nanjing First Hospital, Nanjing Medical University, Nangjing, Jiangsu, China
  • Cao, Changchun, Nanjing Medical University, Sir Run Run Hospital,, Nangjing, Jiangsu, China
  • Wan, Xin, Nanjing First Hospital, Nanjing Medical University, Nangjing, Jiangsu, China
Background

Dysorder of tryptophan metabolism catalyzed by indoleamine-2, 3-dioxygenase (IDO) is common in chronic kidney disease which manifests as increased kidney fibrosis. IDO is also reported to be involved in fibrosis of other organs while little is known about correlations of IDO and fibrosis in kidney disease.

Methods

Wild type (WT) mice and IDO-/- mice were employed. Mice in Sham group underwent exposure of renal artery while mice in AKI group received unique renal artery ischemia-reperfusion injury (IRI) and the contralateral kidney was removed at day 13 after IRI. Samples were collected at day 14. Kidney function, morphology and fibrosis markers were analyzed. Prostaglandin E2 (PGE2) was administrated to WT AKI mice. Clinically, a total of 115 CKD patients and 30 non-CKD patients were recruited. IDO was calculated by the ratio of kynurenine and tryptophan. Correlations between indicators were analyzed. The ROC curve was also performed.

Results

WT AKI mice revealed elevated expression of IDO and worse kidney function. PAS staining exhibited less loss of tubular epithelial cells and atrophy tubules in IDO-/- AKI mice. Additionally, fibrosis markers, including α-SMA, fibronectin and vimentin, were more severer in WT AKI mice. GSK-3β and β-catenin were significantly decline in IDO-/- AKI mice. On top of that, PGE2 administration revealed reduced IDO expression and decreased levels of GSK-3β and β-catenin resulting in lower expressions of α-SMA, fibronectin and vimentin in WT AKI mice. In patients, IDO had negative correlations with eGFR (r=-0.742, p<0.001). Further, the linear regression showed IDO was an independent influence factor of eGFR. ROC curve showed the area under the ROC curve was 0.825 for IDO.

Conclusion

IDO could activate Wnt/β-catenin pathway to induce kidney fibrosis. PGE2 could ameliorate kidney fibrosis via inhibiting IDO expression.

Scatter plot of IDO associated with eGFR