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Updated: Jun 18, 2026

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
The serum and glucocorticoid-regulated kinase 1 in hypoxic renal injury
Krisztina Rusai1, Bettina Wagner, Marcel Roos
1First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Abstract:
The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a serine threonine protein kinase activated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway and counteracting apoptosis. Protein expression and activation of SGK1 are increased in various models of cell stress. The present study explored the role of SGK1 in renal hypoxia/ischemia induced apoptosis. HEK 293 cells were exposed in vitro to hypoxia/reoxygenation (H/R), which increased SGK1 transcript levels, SGK1 protein abundance and SGK1 phosphorylation. H/R injury further enhanced the percentage of apoptotic cells, an effect significantly blunted by prior SGK1 overexpression. In vivo renal ischemia/reperfusion (I/R) injury increased SGK1 transcript levels and SGK1 protein abundance. I/R enhanced apoptosis, an effect significantly more pronounced in gene targeted mice lacking SGK1. In conclusion, SGK1 is up-regulated and counteracts apoptosis following H/R in vitro and ischemia In vivo.
Insights
Serum- and glucocorticoid-inducible kinase 1 (SGK1) protects against cell death. This study found SGK1 counteracts apoptosis during kidney hypoxia and ischemia, highlighting its protective role in renal injury.
Area of Science:
- Molecular Biology
- Cell Biology
- Renal Physiology
Background:
- Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a kinase activated by the PI3-kinase pathway.
- SGK1 activation and expression increase under cellular stress conditions.
- SGK1 is known to counteract apoptosis.
Purpose of the Study:
- To investigate the role of SGK1 in apoptosis induced by renal hypoxia/ischemia.
- To determine if SGK1 expression and activation are altered during renal ischemia-reperfusion injury.
Main Methods:
- In vitro experiments using HEK 293 cells exposed to hypoxia/reoxygenation (H/R).
- In vivo studies utilizing gene-targeted mice lacking SGK1 subjected to renal ischemia/reperfusion (I/R).
- Analysis of SGK1 transcript levels, protein abundance, phosphorylation, and apoptosis rates.
Main Results:
- In vitro H/R increased SGK1 transcript, protein levels, and phosphorylation in HEK 293 cells.
- Overexpression of SGK1 significantly reduced apoptosis in cells exposed to H/R.
- In vivo I/R injury elevated SGK1 transcript and protein levels in the kidney.
- Apoptosis following I/R was significantly exacerbated in mice lacking SGK1.
Conclusions:
- SGK1 is upregulated in response to both in vitro and in vivo renal ischemia.
- SGK1 plays a crucial protective role by counteracting apoptosis during renal hypoxic/ischemic injury.
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