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Effects of BSF on Podocyte Apoptosis via Regulating the ROS-Mediated PI3K/AKT Pathway in DN
Fang-Qiang Cui1, Yue-Fen Wang1, Yan-Bin Gao2,3
1Department of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing 100010, China.
Abstract:
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The ROS-mediated PI3K/AKT pathway plays a key role in podocyte apoptosis and DN progression. Our previous study demonstrated that Baoshenfang (BSF) can decrease proteinuria and attenuate podocyte injury. However, the effects of BSF on podocyte apoptosis induced by the ROS-mediated PI3K/AKT pathway remain unclear. Herein, in vivo and in vitro studies have been performed. In our in vivo study, BSF significantly decreased 24-h urinary protein, serum creatinine, and blood urea nitrogen levels in DN mice. Meanwhile, BSF significantly inhibited oxidative stress and podocyte apoptosis in our in vivo and in vitro studies. Moreover, BSF significantly decreased the inhibition of the PI3K/AKT pathway induced by HG in DN. More importantly, the effects of BSF on podocyte apoptosis were reversed by PI3K siRNA transfection. In conclusion, BSF can decrease proteinuria and podocyte apoptosis in DN, in part through regulating the ROS-mediated PI3K/AKT pathway.
Insights
Baoshenfang (BSF) reduces proteinuria and podocyte apoptosis in diabetic nephropathy (DN). It works by regulating the ROS-mediated PI3K/AKT pathway, offering a potential therapeutic strategy for DN and end-stage renal disease (ESRD).
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Diabetic nephropathy (DN) is a primary cause of end-stage renal disease (ESRD).
- Reactive oxygen species (ROS)-mediated PI3K/AKT pathway is crucial in podocyte apoptosis and DN progression.
- Previous research indicated Baoshenfang (BSF) reduces proteinuria and podocyte injury, but its mechanism on the ROS-mediated PI3K/AKT pathway in DN was unclear.
Purpose of the Study:
- To investigate the effects of Baoshenfang (BSF) on podocyte apoptosis induced by the ROS-mediated PI3K/AKT pathway in diabetic nephropathy (DN).
- To elucidate the therapeutic potential of BSF in DN by examining its impact on oxidative stress and the PI3K/AKT signaling pathway.
Main Methods:
- Conducted in vivo studies using diabetic nephropathy (DN) mouse models and in vitro studies on podocytes.
- Assessed 24-h urinary protein, serum creatinine, and blood urea nitrogen levels.
- Evaluated oxidative stress, podocyte apoptosis, and the PI3K/AKT pathway, including experiments with PI3K siRNA.
Main Results:
- Baoshenfang (BSF) significantly reduced proteinuria, serum creatinine, and blood urea nitrogen in DN mice.
- BSF treatment markedly inhibited oxidative stress and podocyte apoptosis in both in vivo and in vitro models.
- BSF reversed high glucose-induced inhibition of the PI3K/AKT pathway, with effects on apoptosis being PI3K-dependent.
Conclusions:
- Baoshenfang (BSF) effectively decreases proteinuria and podocyte apoptosis in diabetic nephropathy (DN).
- BSF exerts its protective effects, at least in part, by modulating the ROS-mediated PI3K/AKT signaling pathway.
- These findings highlight BSF as a promising therapeutic agent for managing DN and preventing ESRD.
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