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Updated: Aug 21, 2026
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells
1School of Public Health, University of Texas-Houston Health Science Center, Houston, TX 77030, USA. dking@mdanderson.org
Abstract:
Vancomycin (VAN) is a glycopeptide antibiotic used to treat gram-positive infections. Nephrotoxicity is a common side effect observed with vancomycin therapy. However, the mechanism of vancomycin-induced nephrotoxicity has not been fully characterized. In this study we examined the effect of vancomycin on cellular proliferation in renal proximal tubule cells. A dose- and time-dependent increase in cell number and total cellular protein was observed following vancomycin exposure. Vancomycin exposure also caused an increase in BrdU incorporation followed by the accumulation of renal proximal tubule cells in G(2)/M phase of the cell cycle. These effects were inhibited by pretreatment with the mitogen-activated protein kinase inhibitor, PD098059, suggesting an association between the cell proliferative effect of VAN and the induction of the mitogen-activated protein kinase signaling pathway. Mitochondrial function in renal proximal tubule cells was assessed using oxygen consumption and ATP concentrations. We observed an increase in oxygen consumption and ATP concentrations following short-term exposure to vancomycin. Together, our data suggest that vancomycin treatment produces alterations in mitochondrial function that coincide with a cell proliferative response in renal proximal tubule epithelial cells.
Insights
Vancomycin (VAN) exposure increases renal proximal tubule cell proliferation and alters mitochondrial function. These effects, linked to the MAPK pathway, suggest VAN may impact kidney cell dynamics.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Vancomycin (VAN) is crucial for treating Gram-positive infections.
- Nephrotoxicity is a significant side effect of VAN therapy.
- The precise mechanisms underlying VAN-induced nephrotoxicity remain unclear.
Purpose of the Study:
- To investigate the effects of VAN on renal proximal tubule (RPT) cell proliferation.
- To explore the role of the mitogen-activated protein kinase (MAPK) signaling pathway.
- To assess VAN's impact on mitochondrial function in RPT cells.
Main Methods:
- Exposure of RPT cells to varying doses and durations of VAN.
- Assessment of cell proliferation using cell counting, total protein, and BrdU incorporation.
- Cell cycle analysis to determine phase distribution (G(2)/M).
- Inhibition studies using the MAPK inhibitor PD098059.
- Measurement of mitochondrial respiration (oxygen consumption) and ATP levels.
Main Results:
- VAN exposure led to a dose- and time-dependent increase in RPT cell number and protein content.
- VAN induced BrdU incorporation and G(2)/M cell cycle arrest.
- PD098059 pretreatment mitigated VAN-induced proliferation.
- Short-term VAN exposure increased mitochondrial oxygen consumption and ATP production.
Conclusions:
- VAN treatment stimulates a cell proliferative response in RPT cells.
- The MAPK signaling pathway is implicated in VAN's proliferative effects.
- Alterations in mitochondrial function accompany VAN-induced cell proliferation in RPT cells.
