Activation of the IL-6/STAT3 pathway contributes to the pathogenesis of membranous nephropathy and is a target for Mahuang Fuzi and Shenzhuo Decoction (MFSD) to repair podocyte damage - 27/04/24
, Baoli Liu a, b, ⁎ Abstract |
Background |
Primary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear.
Methods |
Serum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury. RNA-seq was used to screen the possible targets of MFSD, and the effect of MFSD targeting IL-6/STAT3 was further verified by combining the experimental results. Finally, the efficacy of tocilizumab in PHN rats was observed.
Results |
Serum IL-6 levels were significantly higher in PMN patients than in healthy subjects. These levels significantly decreased in patients in remission after MFSD treatment. MFSD treatment improved laboratory indicators in PHN rats, as well as glomerular filtration barrier damage and podocyte marker protein expression. Renal transcriptome changes showed that MFSD-targeted differential genes were enriched in JAK/STAT and cytokine-related pathways. MFSD inhibits the IL6/STAT3 pathway in podocytes. Additionally, MFSD significantly reduced serum levels of IL-6 and other cytokines in PHN rats. However, treatment of PHN with tocilizumab did not achieve the expected effect.
Conclusion |
The IL-6/STAT3 signaling pathway is activated in podocytes of experimental membranous nephropathy. MFSD alleviates podocyte damage by inhibiting the IL-6/STAT3 pathway.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | This article shows the changes of serum IL-6 in membranous nephropathy patients with different outcomes after MFSD treatment. |
• | Through the passive heymann nephritis in rats, the authors verified the MFSD effect on podocyte damage repair. |
• | Based on RNA-seq analysis, IL-6/STAT3 pathway was found to be an important target of MFSD, verified by multiple experiments. |
Keywords : Membranous nephropathy, Mahuang Fuzi and Shenzhuo Decoction, IL-6/STAT3, Podocyte, RNA-seq
Plan
Vol 174
Article 116583- mai 2024 Retour au numéro
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