Bone mesenchymal stem cells ameliorate ischemia/reperfusion-induced damage in renal epithelial cells via microRNA-223
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Updated: Feb 28, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Xiaopeng Yuan1, Xiaoping Wang2, Chuanbao Chen2
1Third Division of Organ Transplant Center, Eastern Campus of First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510700, People's Republic of China. transplantyuan@163.com.
Background:
Recent studies have indicated that microRNA-223 (miR-223) plays a role in the tissue-protective effect of mesenchymal stem cells (MSCs). NLR family-pyrin domain containing 3 (NLRP3) was reported to affect a renal ischemia/reperfusion (I/R) injury by exerting a direct effect on the renal tubular epithelium. Therefore, we investigated how miR-223 and NLRP3 might function in kidneys exposed to conditions of ischemia and subsequent reperfusion.
Methods:
Hypoxia/reoxygenation (H/R) murine renal tubular epithelial cells (RTECs) were cocultured with either MSCs or hypoxia-pretreated MSCs (htMSCs), after which the RTECs were examined for their viability and evidence of apoptosis. Next, miR-223 expression in the MSCs was downregulated to verify that MSCs protected RTECs via the transport of miR-223. Kidney I/R KM/NIH mouse models were created and used for in vivo studies.
Results:
The results showed that coculture with MSCs significantly increased the viability of RTECs and decreased their rates of apoptosis. The levels of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) in samples of coculture supernatants were higher than those in samples of non-coculture supernatants. A bioinformatics analysis revealed a targeting relationship between miR-223 and NLRP3. A dual luciferase assay showed that miR-223 inhibited NLRP3 expression. The htMSCs displayed a protective function associated with an upregulation of miR-223 as induced by Notch1 and the downregulation of NLRP3. Conversely, inhibition of miR-223 impeded the protective effect of MSCs. In the I/R mouse models, injection of either MSCs or htMSCs ameliorated the damage to kidney tissue, while suppression of miR-223 expression in MSCs reduced their protective effect on mouse kidneys.
Conclusions:
Our results demonstrate that miR-223 and NLRP3 play important roles in the treatment of renal tissue injuries with transplanted MSCs.
Insights
Mesenchymal stem cells (MSCs) protect kidneys from ischemia/reperfusion injury by transferring microRNA-223 (miR-223), which inhibits NLRP3. This highlights miR-223 and NLRP3 as key targets for treating renal injuries.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Nephrology
Background:
- Mesenchymal stem cells (MSCs) show tissue-protective effects.
- MicroRNA-223 (miR-223) is implicated in MSC-mediated protection.
- NLRP3 inflammasome activation contributes to renal ischemia/reperfusion (I/R) injury.
Purpose of the Study:
- To investigate the roles of miR-223 and NLRP3 in MSC-based treatment of renal I/R injury.
- To determine if miR-223 transfer mediates the protective effects of MSCs.
- To elucidate the molecular mechanisms underlying MSCs' therapeutic potential in renal I/R.
Main Methods:
- Co-culture of renal tubular epithelial cells (RTECs) with MSCs or hypoxia-pretreated MSCs (htMSCs) under hypoxia/reoxygenation (H/R) conditions.
- Assessment of RTEC viability and apoptosis.
- Downregulation of miR-223 in MSCs to confirm its role in protection.
- In vivo studies using a mouse model of kidney I/R injury.
- Bioinformatics analysis and dual luciferase assays to confirm miR-223 targeting of NLRP3.
Main Results:
- MSC co-culture enhanced RTEC viability and reduced apoptosis, increasing levels of HGF, IGF-1, TGF-β, and VEGF.
- miR-223 was found to directly inhibit NLRP3 expression.
- htMSCs showed increased miR-223 and decreased NLRP3, conferring greater protection.
- Inhibition of miR-223 diminished the protective effects of MSCs in vitro and in vivo.
- MSC transplantation ameliorated kidney damage in I/R mouse models, with miR-223 suppression reducing this benefit.
Conclusions:
- miR-223 plays a critical role in the renoprotective effects of transplanted MSCs.
- The miR-223/NLRP3 axis is a key mechanism in MSC-mediated therapy for renal I/R injury.
- Targeting miR-223 and NLRP3 represents a promising therapeutic strategy for kidney diseases.
