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Updated: Jan 5, 2026
Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions
Published on: June 13, 2025
Sirt6 attenuates hypoxia-induced tubular epithelial cell injury via targeting G2/M phase arrest
Zhao Gao1,2, Xinghua Chen1, Yanqin Fan1
1Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Abstract:
Acute kidney injury (AKI) is a condition that has a high incidence and death rate. Unfortunately, the kidney may not recover completely after AKI, which then develops to chronic kidney disease (CKD). Therefore, it is necessary to identify potential curative targets to avoid its development to CKD. As an NAD+ -dependent deacetylase, sirtuin 6 (Sirt6) has been linked to different types of biological processes. In the present work, our group investigated the role of Sirt6 in tubular epithelial cells (TECs) under hypoxic stress. Sirt6 expression was examined in mouse kidney following ischemia/reperfusion (IR) injury and hypoxia-challenged TECs. Using Sirt6 plasmid and small interfering RNA, we also investigated how, in regard to inflammation and epithelial-to-mesenchymal transition, Sirt6 affects hypoxia-triggered injury. In addition, cell cycle was detected in hypoxia-challenged TECs. Sirt6 was downregulated in the kidney of mice with IR injury and hypoxia-challenged TECs. Consequently, Sirt6 depletion aggravated hypoxia-induced injury and G2/M phase arrest. Sirt6 overexpression attenuated hypoxia-triggered damage and G2/M phase arrest in TECs. Sirt6 prevented hypoxia-triggered TEC damage via suppressing G2/M phase arrest. Thus, Sirt6 is a possible candidate for alleviating the effects of kidney injury.
Insights
Sirtuin 6 (Sirt6) protects against acute kidney injury (AKI) by preventing cell cycle arrest in kidney tubular epithelial cells (TECs). Restoring Sirt6 levels may offer a therapeutic strategy to prevent AKI progression to chronic kidney disease (CKD).
Area of Science:
- Nephrology
- Molecular Biology
- Cellular Biology
Background:
- Acute kidney injury (AKI) has high incidence and mortality, often progressing to chronic kidney disease (CKD).
- Identifying therapeutic targets to prevent AKI progression is crucial.
- Sirtuin 6 (Sirt6), an NAD+-dependent deacetylase, is implicated in various biological processes.
Purpose of the Study:
- To investigate the role of Sirt6 in tubular epithelial cells (TECs) under hypoxic stress.
- To determine if Sirt6 can mitigate hypoxia-induced kidney injury and prevent progression to CKD.
Main Methods:
- Examined Sirt6 expression in mouse kidneys after ischemia/reperfusion (IR) injury and in hypoxia-challenged TECs.
- Utilized Sirt6 plasmid and small interfering RNA to modulate Sirt6 levels in TECs.
- Assessed inflammation, epithelial-to-mesenchymal transition, and cell cycle progression (G2/M phase arrest) in response to Sirt6 manipulation under hypoxic conditions.
Main Results:
- Sirt6 expression was downregulated in mouse kidneys with IR injury and in hypoxia-challenged TECs.
- Sirt6 depletion exacerbated hypoxia-induced TEC injury and G2/M phase arrest.
- Sirt6 overexpression attenuated hypoxia-triggered damage and suppressed G2/M phase arrest in TECs.
Conclusions:
- Sirt6 plays a protective role in TECs against hypoxia-induced damage by preventing G2/M phase arrest.
- Sirt6 is a potential therapeutic target for alleviating kidney injury and preventing its progression to CKD.