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Updated: Mar 6, 2026
Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions
Published on: June 13, 2025
Ochratoxin A induced premature senescence in human renal proximal tubular cells
Xuan Yang1, Sheng Liu1, Chuchu Huang1
1Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Abstract:
Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP). Cell cycle arrest and cell shape alternations also confirmed senescence. In addition, telomere analysis by RT-qPCR allowed us to classify OTA-induced senescence as a premature senescence. Western blot assays showed that the p53-p21 and the p16-pRB pathways and the ezrin-associated cell spreading changes were activated during the OTA-induced senescence of HKC. In conclusion, our results demonstrate that OTA promotes the senescence of HKC through the p53-p21 and p16-pRB pathways. The understanding of the mechanisms of OTA-induced senescence is critical in determining the role of OTA in cytotoxicity and its potential carcinogenicity.
Insights
Ochratoxin A (OTA) induces premature kidney cell senescence via p53-p21 and p16-pRB pathways. This study clarifies OTA
Area of Science:
- Nephrotoxicity
- Cellular Senescence
- Molecular Toxicology
Background:
- Ochratoxin A (OTA) is a nephrotoxic mycotoxin with largely unknown effects on renal senescence.
- Human renal proximal tubular cells (HKC) are a key model for studying kidney physiology and pathology.
- The precise mechanisms by which OTA induces kidney damage, particularly senescence, remain unclear.
Purpose of the Study:
- To investigate whether Ochratoxin A (OTA) can induce renal senescence in human renal proximal tubular cells (HKC) at sublethal doses.
- To elucidate the molecular mechanisms underlying OTA-induced kidney cell senescence.
- To determine the role of specific cellular pathways in OTA toxicity.
Main Methods:
- Exposure of HKC to a sublethal dose of Ochratoxin A (OTA).
- Assessment of senescent phenotype using β-galactosidase staining and analysis of senescence-associated secretory phenotype (SASP).
- Evaluation of cell cycle arrest, cell morphology changes, telomere length (RT-qPCR), and activation of p53-p21 and p16-pRB pathways (Western blot).
Main Results:
- Sublethal OTA exposure induced a significant senescent phenotype in HKC, characterized by increased β-galactosidase activity and SASP.
- OTA-induced senescence was classified as premature senescence based on telomere length analysis.
- Activation of the p53-p21 and p16-pRB signaling pathways was observed, alongside alterations in ezrin-mediated cell spreading.
Conclusions:
- Ochratoxin A (OTA) promotes premature senescence in human renal proximal tubular cells (HKC).
- The p53-p21 and p16-pRB signaling pathways are critical mediators of OTA-induced kidney cell senescence.
- Understanding these mechanisms is vital for assessing OTA's cytotoxicity and carcinogenic potential.
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