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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway
Rong Zheng1, Yueyi Deng, Yiping Chen
1Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Abstract:
Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood. Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex. In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase.
Insights
Astragalus membranaceus, a traditional Chinese medicine, may treat membranous nephropathy (MN) by protecting kidney podocytes. Its active compound, astragaloside IV (AS-IV), reduces podocyte injury and regulates key signaling pathways involved in MN.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome, characterized by podocyte injury.
- Astragalus membranaceus is traditionally used in China to treat MN, with documented benefits for proteinuria.
- The precise mechanism by which Astragalus membranaceus alleviates MN remains unclear.
Purpose of the Study:
- To investigate the therapeutic mechanism of Astragalus membranaceus in a podocyte injury model relevant to MN.
- To elucidate how astragaloside IV (AS-IV), a key component, impacts podocyte damage and signaling pathways.
Main Methods:
- Utilized a complement membranous attack complex-induced podocyte injury model.
- Assessed lactate dehydrogenase (LDH) release as an indicator of cell damage.
- Evaluated podocyte morphology, cytoskeleton integrity, and the phosphorylation status of JNK and ERK1/2.
Main Results:
- Complement attack complex increased LDH release from podocytes; AS-IV inhibited this release dose-dependently.
- AS-IV treatment restored podocyte morphology and reversed cytoskeleton damage.
- AS-IV reduced the phosphorylation of JNK and ERK1/2 pathways induced by complement attack.
Conclusions:
- Astragalus membranaceus may treat MN by protecting podocytes from injury.
- The mechanism involves maintaining podocyte cytoskeleton integrity and modulating mitogen-activated protein kinase (MAPK) signaling.
- AS-IV is a key active compound in Astragalus membranaceus responsible for these protective effects.
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