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Updated: Aug 16, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Mesenchymal stem cells ameliorate cisplatin-induced acute kidney injury via let-7b-5p
Si-Yang Wang1,2, Yue Xu1, Quan Hong1
1Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, 100853, China.
Abstract:
Acute kidney injury (AKI) is a clinically common kidney disease. Age is an important factor that contributes to the susceptibility to AKI. Mesenchymal stem cells (MSCs) are a promising therapy for AKI, and miRNAs in exosomes (Exos) derived from MSCs are an important aspect of MSC treatment. However, the therapeutic effect of miRNA from MSC-derived Exos on AKI and the related mechanism have not been fully clarified. Whether there is a relationship between the mechanisms of senescence for AKI susceptibility and the therapeutic effect of MSCs has not been studied. We compared the degree of cisplatin-induced AKI injury in young and elderly mice and investigated changes in the expression of p53 and markers of DNA damage and apoptosis, which are important in both senescence and AKI. Ageing mice exhibited increased expression of p53 and pro-apoptosis markers. Upregulation of the senescence-associated DNA damage/p53 pathway may be an important susceptibility factor for cisplatin-induced AKI. Treatment with MSCs can reduce the degree of DNA damage and suppress p53 expression and apoptosis. Upon screening for differentially expressed miRNAs, let-7b-5p levels were found to be lower in aged mice than in young mice, and MSC treatment increased let-7b-5p levels. The presence of let-7b-5p in MSC-derived Exos alleviates tubular epithelial cell apoptosis by inhibiting p53, which reduces DNA damage and apoptosis pathway activity. Let-7b-5p downregulation may lead to increased renal AKI susceptibility, thus indicating that this miRNA is a potential driver of the MSC treatment response in AKI.
Insights
Aging increases susceptibility to acute kidney injury (AKI) via the p53 pathway. Mesenchymal stem cell (MSC) therapy, particularly exosomal let-7b-5p, mitigates AKI by inhibiting p53 and reducing apoptosis.
Area of Science:
- Nephrology
- Gerontology
- Molecular Biology
Background:
- Acute kidney injury (AKI) is a common condition, with age significantly increasing susceptibility.
- Mesenchymal stem cells (MSCs) show therapeutic potential for AKI, partly through exosome-mediated delivery of microRNAs (miRNAs).
- The interplay between aging-related senescence mechanisms and MSC therapy for AKI remains unclear.
Purpose of the Study:
- To investigate the role of aging and the senescence-associated p53 pathway in cisplatin-induced AKI susceptibility.
- To explore the therapeutic mechanisms of MSCs in AKI, focusing on exosomal miRNAs.
- To determine if let-7b-5p, a specific miRNA, mediates the protective effects of MSCs against AKI.
Main Methods:
- Comparison of cisplatin-induced AKI severity in young versus aged mice.
- Assessment of p53 expression, DNA damage, and apoptosis markers.
- miRNA profiling in aged and young mice, and analysis of miRNA levels after MSC treatment.
- In vitro experiments to evaluate the effect of let-7b-5p on tubular epithelial cells.
Main Results:
- Aged mice exhibited heightened p53 expression and apoptosis, indicating increased susceptibility to AKI.
- MSC treatment reduced DNA damage, suppressed p53, and decreased apoptosis in aged mice.
- let-7b-5p levels were lower in aged mice and increased following MSC treatment.
- Exosomal let-7b-5p alleviated tubular cell apoptosis by inhibiting p53, reducing DNA damage and apoptosis.
Conclusions:
- The senescence-associated DNA damage/p53 pathway is a key factor in age-related AKI susceptibility.
- MSC-derived exosomal let-7b-5p is a crucial mediator of therapeutic effects in AKI by targeting the p53 pathway.
- let-7b-5p represents a potential therapeutic target and biomarker for AKI treatment response.
