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Kidney Week

Abstract: SA-PO973

CCL20 Blockade Mitigates the Progression of AKI to CKD

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Yoo, Kyung Don, University of Ulsan College of Medicine, Songpa-gu, Korea (the Republic of)
  • Yu, Mi-yeon, Hanyang University, Seongdong-gu, Seoul, Korea (the Republic of)
  • Kim, Kyu hong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Song, Jehun, University of Ulsan College of Medicine, Songpa-gu, Korea (the Republic of)
  • Bae, Jinsuk, University of Ulsan College of Medicine, Songpa-gu, Korea (the Republic of)
  • Lee, Sunhwa, Kangwon National University Hospital, Chuncheon, Kangwon, Korea (the Republic of)
  • Jo, Hyung Ah, Inje University Ilsan Paik Hospital, Goyang, Korea (the Republic of)
  • Kim, Yong Chul, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
  • Lee, Jong Soo, University of Ulsan College of Medicine, Songpa-gu, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
  • Yang, Seung Hee, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
Background

Chronic kidney injury promotes renal inflammation and oxidative stress, highlighting precondition for organ fibrosis. Here, we investigated how chemokine receptor CCR6 and its ligand can alter acute kidney injury (AKI) to chronic kidney disease (CKD).

Methods

Unilateral ischemia-reperfusion injury (uIRI) was induced for 30 minutes in 7- to 8-wk-old male C57BL/6 mice, and the animals were observed for 4 weeks. Meanwhile, rats with 5/6 nephrectomy were performed to evaluate transcriptome changes via RNA sequencing at 8 weeks. In vitro experiments, primary-cultured human tubular epithelial cells (hTECs) were cultured on hypoxia (5% O2, CO2, and 90% N2, 4days) and H2O2-induced oxidative stress (0.125mM, 3 days) conditions with/without CCL20 blocking antibody. In addition, CCR6/CCL20 expressions in kidney tissues of patients with CKD were assessed.

Results

In both animal models, the expression of CCL20 increased as inflammation and fibrosis increased. Therefore, a positive correlation was observed for CCL20 in fibrosis. Furthermore, CCL20 blockade in human tubular epithelial cells ameliorated apoptotic damage in a dose-dependent manner on hypoxia and ROS injury. Interestingly, the CCL20 blockade led to a more significant reduction of intracellular ROS, 8-OHDG, and ICAM-1 level. uIRI provoked CCR6 expression that showed a similar severity as patients with acute kidney disease (AKD) phenotype. We analyzed CCR6/CCL20 expression from 22/18/16 patients with CKD stages 1-2/3/4-5, respectively. Morphometry of CCR6/CCL20 co-expression revealed that CKD stage 3 patients were more likely to possess CCR6 expressions than CKD stage 1-2 patients (10.94% vs. 5.79%, p=0.001). Together, Kidney tissues of CKD patients frequently containing CCL20 cells showed a positive correlation with interstitial inflammation (p=0.001). CCL20/CCR6 activation is associated with uIRI progression, and CCL20 may be an essential contributor.

Conclusion

CCR6/CCL20 inhibition could be a potential therapeutic target for managing AKD progression to CKD.

Funding

  • Other NIH Support