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Updated: Jun 24, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice
Yupeng Jiang1, Feifei Xie1, Xin Lv1
1Department of Nephrology, Xiangya Hospital of Central South University, Changsha, China.
Abstract:
Diabetic kidney disease (DKD) is a major cause of end stage renal diseases worldwide. Despite successive interventions for delaying the progression of DKD, current treatments cannot reverse the pathological progression. Mefunidone (MFD) is a new compound with potent antifibrotic properties, but the effect of MFD on DKD remains unknown. Therefore, we investigated the protective effects of MFD in both models of the db/db type 2 diabetes (T2D) and streptozotocin (STZ)-induced type 1 diabetes (T1D) models. Compared with the model group, MFD treatment significantly reduced pathological changes observed by PAS staining, PASM staining, and Masson staining in vivo. To further elucidate the potential mechanisms, we discovered MFD treatment notably restored podocyte function, alleviated inflammation, abated ROS generation, inhibited the TGF-β1/SAMD2/3 pathway, suppressed the phosphorylation levels of MAPKs (ERK1/2, JNK, and P38), and reduced epithelial-to-mesenchymal transition(EMT). In conclusion, these findings demonstrate the effectiveness of MFD in diabetic nephropathy and elucidate its possible mechanism.
Insights
Mefunidone (MFD) shows protective effects against diabetic kidney disease (DKD) in type 1 and type 2 diabetes models. This antifibrotic compound alleviates pathological changes and offers a potential new treatment for diabetic nephropathy.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease globally.
- Current DKD treatments cannot reverse established pathological progression.
- Mefunidone (MFD) is a novel antifibrotic compound with unknown effects on DKD.
Purpose of the Study:
- To investigate the protective effects of Mefunidone (MFD) in diabetic kidney disease (DKD).
- To explore the underlying mechanisms of MFD's action in DKD models.
Main Methods:
- Utilized db/db type 2 diabetes (T2D) and streptozotocin (STZ)-induced type 1 diabetes (T1D) mouse models.
- Assessed pathological changes using PAS, PASM, and Masson staining.
- Investigated molecular mechanisms including podocyte function, inflammation, ROS, TGF-β1/SAMD2/3 pathway, MAPKs, and epithelial-to-mesenchymal transition (EMT).
Main Results:
- MFD treatment significantly reduced kidney pathological changes in both T1D and T2D models.
- MFD restored podocyte function, reduced inflammation, and decreased ROS generation.
- MFD inhibited the TGF-β1/SAMD2/3 pathway, suppressed MAPK phosphorylation, and reduced EMT.
Conclusions:
- Mefunidone demonstrates significant protective effects against diabetic nephropathy.
- MFD's mechanism involves restoring podocyte function, reducing inflammation and oxidative stress, and inhibiting fibrotic pathways like TGF-β1/SAMD2/3 and EMT.
