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Updated: Sep 24, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Dihydroquercetin/Taxifolin Inhibits METTL3/m6A/PIM2 Expression by Suppressing RIPK2 Phosphorylation Mediated NF-κB
Sheng Shen1,2, Xiao Wang2, Zhongda Li2
1Department of Urinary Nephropathy Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Introduction:
There is a close relationship between oxidative stress and renal ischemia-reperfusion injury (RIRI). Dihydroquercetin (DHQ, also known as Taxifolin) can reduce kidney damage, and suppress cellular damage caused by oxidative stress. This study aimed to investigated the effects and underlying mechanisms of DHQ on RIRI.
Methods:
First, hypoxia/reoxygenation (H/R) treated HK-2 cells were used for RIRI in vitro experiments, and the dosage of DHQ was selected by observing cell viability and lactate dehydrogenase release. The protective effects of DHQ were evaluated by detecting cell apoptosis, reactive oxygen species (ROS) levels, and oxidative stress indicators levels.
Results:
Our data suggested that DHQ inhibited cell apoptosis, ROS levels, and oxidative stress of H/R treated HK-2 cells. PIM2 regulates cell survival and proliferation, and H/R treatment upregulated PIM2 levels. Over-expression of PIM2 partly reversed the effects of DHQ on protecting HK-2 cells after H/R induction, and promoted RIPK2 phosphorylation mediated NF-κB p65 signaling pathway. Additionally, METTL3 is an N6-methyladenosine (m6A) writer, and DHQ suppressed its expression in H/R treated HK-2 cells. METTL3 was enriched in PIM2 mRNA by m6A modification and stabilized the expression of PIM2. As for in vivo experiments, DHQ also inhibited the PIM2 level in mice kidney tissues and alleviated the kidney damage caused by RIRI. These effects were manifested in the reduction of renal injury markers, the reduction of oxidative stress levels, and the results of renal tissue hematoxylin-eosin staining. DHQ also suppressed PIM2 mediated RIPK2 phosphorylation mediated NF-κB p65 signaling pathway in renal tissues.
Conclusion:
Taken together, DHQ inhibited PIM2 levels by suppressing METTL3 mediated m6A modification to protect HK-2 cells from H/R induced injury, and this may be related to the regulation of PIM2 on RIPK2 phosphorylation mediated NF-κB p65 signaling pathway. This study suggested that DHQ may be a promising drug to treat RIRI, and may be useful for finding effective therapeutic targets in RIRI.
Insights
Dihydroquercetin (DHQ) protects against kidney damage from ischemia-reperfusion injury (RIRI) by reducing oxidative stress and apoptosis. DHQ inhibits PIM2 expression via METTL3-mediated m6A modification, offering a potential therapeutic strategy for RIRI.
Area of Science:
- Biochemistry
- Cell Biology
- Nephrology
Background:
- Oxidative stress is closely linked to renal ischemia-reperfusion injury (RIRI).
- Dihydroquercetin (DHQ), also known as Taxifolin, demonstrates potential in mitigating kidney damage and oxidative stress-induced cellular damage.
Purpose of the Study:
- To investigate the protective effects of DHQ against RIRI.
- To elucidate the underlying molecular mechanisms of DHQ's action in RIRI.
Main Methods:
- In vitro experiments utilized hypoxia/reoxygenation (H/R) treated HK-2 cells to model RIRI.
- Assessed DHQ's protective effects by measuring cell apoptosis, reactive oxygen species (ROS) levels, and oxidative stress indicators.
- In vivo studies involved administering DHQ to mice subjected to RIRI to evaluate kidney damage and molecular changes.
Main Results:
- DHQ significantly inhibited cell apoptosis, ROS production, and oxidative stress in H/R-treated HK-2 cells.
- DHQ suppressed PIM2 and METTL3 expression in H/R-treated cells and in mouse kidney tissues.
- DHQ alleviated kidney damage in vivo, reducing renal injury markers and oxidative stress, and inhibiting the PIM2-mediated RIPK2 phosphorylation signaling pathway.
Conclusions:
- DHQ protects against H/R-induced kidney injury by suppressing PIM2 levels through METTL3-mediated m6A modification.
- The protective mechanism involves the regulation of PIM2 on the RIPK2 phosphorylation-mediated NF-κB p65 signaling pathway.
- DHQ shows promise as a therapeutic agent for RIRI and may help identify novel therapeutic targets.
