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Kidney Week

Abstract: FR-PO137

Role of Primary Cilia in Kidney Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Kim, Su-Mi, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Jung-Woo, Seo, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Kim, Dong-Jin, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Song, Suk jong, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Jung, Su Woong, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Yu ho, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Kim, Yang gyun, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Jeong, Kyung-hwan, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Moon, Ju young, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Sangho, Division of Nephrology Department of internal medicine Kyung Hee University College of Medicine, Seoul, Korea (the Republic of)
Background

The primary cilium is an organelle, present at the cell surface and plays a role as an antenna. The primary cilium mediates cell proliferation, differentiation, death, and planar cell polarity. Recently, it has reported that transforming growth factor (TGF)-β receptors are localized and concentrated within the primary cilium in human mesenchymal stem cells. Also, the primary cilium regulates the transdifferentiation into myofibroblast of human adipose progenitor cells. We investigated a role of the primary cilium in renal fibroblast-myofibroblast transdifferentiation through regulating TGF-β1 receptors and the modulating cilia would attenuate interstitial fibrosis in unilateral ureteral obstruction (UUO) model.

Methods

NRK-49F cells were differentiated into myofibroblasts with TGF-β1. Using immunocytochemistry staining and western blot, the primary cilium and the fibroblast-myofibroblast transdifferentiation in NRK-49F cells were studied. UUO was performed to evaluate the interstitial fibrosis.

Results

The primary cilium is crucial for the maintenance of the myofibroblasts phenotype and for TGF-β1-induced Smad phosphorylation. Knock-down of cilia proteins such as SMO, Arl13b, and IFT88 decreased the expression of α-SMA and Smad signaling. TGF-β receptors localized to the primary cilium in NRK-49F cells, especially when the cells are cytokinesis cycle. Colchicine, an inhibitor of microtubule polymerization, and HPI-4, ciliogenesis inhibitor, attenuates cilia growth and TGFβ1-induced fibrosis. In addition, colchicine treatment attenuates interstitial fibrosis in UUO mice kidney.

Conclusion

We provide the evidence that the primary cilium is indispensable for the transdifferentiation from fibroblast into myofibroblast by modulating TGF-β1 receptors. The cilia targeted therapy could be a promising option for attenuating renal fibrosis.