Effects of Jiedu Quyu Zishen Prescription on podocyte damage via CaMK4-mediated cytoskeletal rearrangement in MRL/lpr mice
Objective:To elucidate the mechanism of Jiedu Quyu Zishen Prescription(JP)in treating lupus nephritis(LN)podocyte injury via CaMK4-mediated podocyte cytoskeletal rearrangement.Methods:C57BU6 mice served as controls,while MRU/lpr mice were randomized into model,PDN,and JP groups(n=8).Controls and models were gavaged with distilled water,PDN group received 5 mg/kg prednisone,and JP group received 36 g/kg JP decoction for 8 weeks.Serum anti-double-stranded DNA antibody,tumor necrosis factor α(TNF-α),and interleukin-6(IL-6)levels were assessed by ELISA;urinary proteins by automated biochemistry;renal pathology by HE staining;Ssh1,Limk1,and Cfll mRNA expressions by RT-PCR;nephrin,synaptopodin,F-actin,G-actin,and CaMK4 expressions by immunofluorescence staining.MPC-5,stimulated with R848 to mimic lupus conditions,were treated with control-serum or JP-serum for 12 h.Cell viability,apoptosis,intracellular calcium,and CaMK4 were assessed.Results:JP group exhibited significantly lower serum anti-dsDNA antibody,TNF-α,IL-6 levels(P＜0.01),reduced urinary protein levels(P＜0.01),alleviates kidney pathology injury,upregulated nephrin and synaptopodin,and increased cytoskeletal stability transcription factors.Renal F-actin expression increased,F/G-actin ratio rebounded,while CaMK4 expression decreased.R848 induced apoptosis in MPC-5,intracellular calcium increase(P＜0.01),and elevated CaMK4;JP-serum reduced the apoptosis,intracellular calcium(P＜0.01),and CaMK4 expression.Conclusion:JP may regulate CaMK4-mediated podocyte cytoskeletal rearrangement,ameliorating LN podocyte damage and SLE condition.
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