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Kidney Week

Abstract: FR-PO549

Anoctamin 3 Enhances Cystogenesis and Ciliary Dosage of Polycystins by cAMP Signaling in Renal Cilia

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Author

  • Xu, Tao, Shanghai Jiaotong University School of Medicine Affiliated Shanghai Sixth People's Hospital, Shanghai, China
Background

Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy which is characterized by abnormal tubular epithelial proliferation and fluid secretion.We reported Anoctamin1(ANO1),one of chlorine channels family could accelerate both cilia formation and cilia trafficking of polycystins. Anoctamin3(ANO3) was recently shown to be involved in ADPKD progression in our research.

Methods

1.Real-time RCR,IHC and Western blot to detect expression of ANO3 in kidney tissue of ADPKD patients and normal kidndy.
2.3D culture to vertify the function of ANO3 in cysts formation with siANO3.
3.Super-resolution 3D structured illumination microscopy and co-IF to investigate ANO3 location and the impact of ANO3 on PC2 by siRNA in cilia.
4.MQAE to detect chloride ion flow by shANO3 and ad-ANO3 treating in ADPKD cells.
5.MRI to calculate the separates normal tubule space from cystic fluid area (Cyst fluid SA ) in PKD1 flox/floxCAG-creER+ mice.

Results

1.ANO3 located in renal tubules and cyst and upregulated in human and mouse ADPKD kidneys.
2.siANO3 could inhibited cysts formation.
3.ANO3 was puncta-like localization on cilia membrane and siANO3 increased the cilia length and the expression of PC2.
4.Chloride ion flow was lower by shANO3 treating than ad-ANO3 in ADPKD cells.
5.Cyst fluid SA in PKD1 flox/floxCAG-creER+ mice was significantly decrease than which in PKD1RC/RC mice.

Conclusion

ANO3 may aggravate ADPKD by regulating the renal cilia length and PC2 expression through cAMP signaling and provide mechanistic insights regarding the therapeutic potential of ANO3 pathway.