Mitochondria are essential for eukaryotic cell activity and function, and their dysfunction is associated with the development and progression of renal diseases. In recent years, there has been a rapid development in mitochondria‐targeting pharmacological strategies as mitochondrial biogenesis, morphology, and function, as well as dynamic changes in mitochondria, have been studied in disease states. Mitochondria‐targeting drugs include nicotinamide mononucleotide, which supplements the NAD+ pool; mitochondria‐targeted protective compounds, such as MitoQ; the antioxidant coenzyme, Q10; and cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. However, traditional drugs targeting mitochondria have limited clinical applications due to their inability to be effectively absorbed by mitochondria in vivo and their high toxicity. Recently, SS‐31, a mitochondria‐targeting antioxidant, has received significant research attention as it decreases mitochondrial reactive oxygen species production and prevents mitochondrial depolarization, mitochondrial permeability transition pore formation, and Ca²⁺‐induced mitochondrial swelling, and has no effects on normal mitochondria. At present, few studies have evaluated the effects of SS‐31 against renal diseases, and the mechanism underlying its action is unclear. In this review, we first discuss the pharmacokinetics of SS‐31 and the possible mechanisms underlying its protective effects against renal diseases. Then, we analyze its renal disease‐improving effects in various experimental models, including animal and cell models, and summarize the clinical evidence of its benefits in renal disease treatment. Finally, the potential mechanism underlying the action of SS‐31 against renal diseases is explored to lay a foundation for future preclinical studies and for the evaluation of its clinical applications.

Background: Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. Methods: We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. Results: After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. Conclusions: hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.

Human placenta-derived mesenchymal stem cells (pMSCs) are considered a good source for cell therapy. The purpose of this study was to observe whether the transplantation of human pMSCs would affect the treatment of lupus nephritis (LN)-prone MRL/lpr mice. Multiple injections (at the 16th, 18th, and 20th week of age) of 1 × 10⁶pMSCs were administered. Urine was collected to evaluate proteinuria and urine creatinine levels. Blood was collected for the measurement of serum antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody levels. Renal tissues were collected for histological staining and examination by light and electron microscopy quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot. The results confirmed that pMSC treatment reduced the severity of 24-h proteinuria, decreased the production of anti-dsDNA antibodies, and ameliorated renal pathological changes in MRL/lpr mice. Furthermore, pMSCs reduced renal inflammation by inhibiting the expression of nuclear factor kappa B (NF-κB) and then downregulating the expression of tumor necrosis factor-α(TNF-α), intercellular cell adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1). Therefore, our present study demonstrated a protective effect of pMSCs against renal injury and inflammation in MRL/lpr mice.