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Abstract: FR-PO682

Prescribed Chinese Herbal Medicine, Shen Ping Decoction, Blocks Activation of Human Mesangial Cells Induced by Different Pathogenic Mechanisms

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Zhang, Xianwen, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Huang, Zhi qiang, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Wang, Lin, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Hall, Stacy D., UAB, Birmingham, Alabama, United States
  • Julian, Bruce A., University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Chen, Yiping, longhua hospital, SHANGHAI, China
  • Novak, Jan, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

Mesangioproliferative glomerular diseases are characterized by increased proliferation of mesangial cells (MC), often due to the activation by PDGF and/or angiotensin II (AII). Shen Ping decoction (SP), an herbal medicine, has been prescribed to treat IgA nephropathy (IgAN) in China for decades; SP treatment effectively reduces proteinuria and stabilizes renal function. To investigate the pharmaceutical mechanisms of SP, we assessed the effects of SP in our model of primary human MC using MC activators PDGF-BB or AII.

Methods

MCs were treated using PDGF-BB for 15 min with or without SP. Phosphorylation of PDGF receptor-β (PGDFR-β), its down-stream signaling, and a TAM-family kinase Axl were assessed by Western blotting using MC lysates. Binding of biotylated PDGF-BB to its receptor was measured with or without SP. Cellular proliferation was determined using BrdU uptake. MCs were also treated with AII for 15 min with or without SP and transactivation of EGFR by AII was assessed.

Results

SP inhibited proliferation of MCs induced by PDGF-BB in a dose-dependent manner. SP blocked binding of PDGF to its receptor, thus inhibiting phosphorylation of PDGFR-β. Activation of down-stream signaling, including phosphorylation of ERK1/2 and AKT, was also blocked by SP. Moreover, SP inhibited PDGF-induced transactivation of TAM-family kinase Axl. Phosphorylation of EGFR in MCs was activated by AII treatment and was inhibited by SP in a dose-dependent manner. Activation of EGFR down-stream signaling, including ERK1/2 and AKT, was also inhibited.

Conclusion

Chinese herbal medicine SP blocked MC activation induced by PDGF-BB or AII through inhibition of multiple signaling pathways. These findings thus explain some of the mechanisms of SP treatment to benefit patients with IgAN.

Funding

  • NIDDK Support