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Ahnak is required to balance calcium ion homeostasis and smooth muscle development in the urinary system
Jong-Min Lee1, Tae-Yang Lim1, Sang-Bin Oh1
1Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, 03722, Korea.
Insights
Neuroblast differentiation-associated protein Ahnak is crucial for kidney and ureter development. Ahnak deficiency in mice leads to hydronephrosis and impaired calcium homeostasis, highlighting its role in urinary system function.
Area of Science:
- Developmental Biology
- Nephrology
- Molecular Biology
Background:
- Renal abnormalities like hydronephrosis and hydroureter are linked to genetic factors.
- Nonobstructive hydronephrosis pathogenesis requires identification of key target genes.
- Ahnak (neuroblast differentiation-associated protein) is implicated in calcium homeostasis.
Purpose of the Study:
- To investigate the role of Ahnak in kidney and ureter development and function.
- To analyze the impact of Ahnak deficiency on urinary system morphogenesis and calcium balance.
Main Methods:
- Examined Ahnak localization in developing mouse kidneys and ureters.
- Performed RNA-sequencing and calcium imaging in wild-type and Ahnak knockout (KO) mice.
- Analyzed gene expression changes and ureteral peristalsis in Ahnak KO mice.
Main Results:
- Ahnak was localized in developing mouse kidneys and ureter.
- Ahnak KO mice exhibited hydronephrosis, hydroureter, and disrupted calcium homeostasis.
- Downregulation of 'Channel Activity' and 'Cellular Calcium Ion Homeostasis' genes observed in KO kidneys and ureters.
- Reduced ureteral smooth muscle peristalsis in Ahnak KO mice.
Conclusions:
- Ahnak is essential for normal kidney and ureter development.
- Disrupted calcium homeostasis due to Ahnak deficiency contributes to renal disease.
- Ahnak plays a pivotal role in maintaining urinary system function through calcium regulation.
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.
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