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Updated: Sep 20, 2026
Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
Published on: June 20, 2018
Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure
Pilar Justo1, Ana Sanz, Corina Lorz
1Fundación Jiménez Díaz, IRSIN, Madrid, Spain.
Background:
Apoptosis contributes to tubular cell loss in the course of renal injury. However, the mechanisms regulating tubular cell apoptosis are not well understood. Smac/Diablo is a mitochondrial protein that is released to the cytosol during apoptosis, where it blocks the antiapoptotic activity of inhibitor of apoptosis proteins (IAPs).
Methods:
We have studied the regulation of Smac/Diablo mRNA and protein expression in murine toxic acute tubular necrosis, and in cultured tubular epithelial cells exposed to the lethal cytokine tumor necrosis factor (TNF).
Results:
Folic acid-induced acute renal failure was associated with tubular cell apoptosis. Smac/Diablo mRNA and protein levels increased by 50% at 24 hours. TNF, a cytokine whose renal expression increases in folic acid nephropathy, induced apoptosis in cultured tubular epithelial cells in a time-dependent manner. In addition, TNF increased the mRNA and protein expression of Smac/Diablo.
Conclusion:
These findings support the concept that regulation of Smac/Diablo mRNA and protein expression is a mechanism by which lethal stimuli amplify their lethal potential in renal cells.
Insights
In renal injury, Smac/Diablo protein levels rise, amplifying cell death signals. This study reveals how Smac/Diablo mRNA and protein expression are regulated during kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Death Research
Background:
- Apoptosis, or programmed cell death, is a key factor in tubular cell loss during kidney injury.
- The precise mechanisms controlling tubular cell apoptosis remain incompletely understood.
- Smac/Diablo, a mitochondrial protein, promotes apoptosis by inhibiting IAPs (inhibitor of apoptosis proteins) in the cytosol.
Purpose of the Study:
- To investigate the regulation of Smac/Diablo mRNA and protein expression in the context of kidney injury.
- To examine the role of tumor necrosis factor (TNF) in tubular cell apoptosis and Smac/Diablo expression.
Main Methods:
- Studied Smac/Diablo expression in murine models of toxic acute tubular necrosis.
- Analyzed Smac/Diablo regulation in cultured tubular epithelial cells exposed to TNF.
- Quantified Smac/Diablo mRNA and protein levels following folic acid-induced renal failure and TNF treatment.
Main Results:
- Folic acid-induced acute renal failure demonstrated increased tubular cell apoptosis.
- Smac/Diablo mRNA and protein levels elevated by 50% within 24 hours in the injury model.
- TNF exposure induced time-dependent apoptosis in tubular cells and upregulated Smac/Diablo expression.
Conclusions:
- The findings support the role of Smac/Diablo regulation in amplifying lethal stimuli effects on renal cells.
- Regulation of Smac/Diablo expression is a significant mechanism in the progression of renal cell apoptosis.
- This study enhances understanding of molecular pathways involved in kidney injury and cell death.
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