Ahnak is required to balance calcium ion homeostasis and smooth muscle development in the urinary system

Jong Min Lee, Tae Yang Lim, Sang Bin Oh, Seung Jun Lee, Yun Soo Bae, Han Sung Jung

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Various renal abnormalities, including hydronephrosis, polycystic kidney disease, and hydroureter, have been reported, and these abnormalities are present in DiGeorge syndrome, renal dysplasia, and acute kidney failure. Previous studies have shown that various genes are associated with renal abnormalities. However, the major target genes of nonobstructive hydronephrosis have not yet been elucidated. Results: We examined neuroblast differentiation-associated protein Ahnak localization and analyzed morphogenesis in developing kidney and ureter. To investigated function of Ahnak, RNA-sequencing and calcium imaging were performed in wild type and Ahnak knockout (KO) mice. Ahnak localization was confirmed in the developing mouse kidneys and ureter. An imbalance of calcium homeostasis and hydronephrosis, which involves an expanded renal pelvis and hydroureter, was observed in Ahnak KO mice. Gene Ontology enrichment analysis on RNA-seq results indicated that ‘Channel Activity’, ‘Passive Transmembrane Transporter Activity’ and ‘Cellular Calcium Ion Homeostasis’ were downregulated in Ahnak KO kidney. ‘Muscle Tissue Development’, ‘Muscle Contraction’, and ‘Cellular Calcium Ion Homeostasis’ were downregulated in Ahnak KO ureter. Moreover, peristaltic movement of smooth muscle in the ureter was reduced in Ahnak KO mice. Conclusions: Abnormal calcium homeostasis causes renal disease and is regulated by calcium channels. In this study, we focused on Ahnak, which regulates calcium homeostasis in several organs. Our results indicate that Ahnak plays a pivotal role in kidney and ureter development, and in maintaining the function of the urinary system.

Original languageEnglish
Article number108
JournalCell and Bioscience
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Funding Information:
The National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF-2022R1A2B5B03001627 and NRF-2021R1A2C1005506) supported this work.

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Ahnak
  • Cellular calcium ion homeostasis
  • Hydronephrosis
  • Hydroureter
  • Kidney
  • Muscle development
  • Ureter

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