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Abstract: SA-PO215

The Melanocortin-1 Receptor Protects Podocytes by Downregulating the Epidermal Growth Factor Receptor

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology


  • Bergwall, Lovisa, University of Gothenburg, Gothenburg, Sweden
  • Elvin, Johannes, University of Gothenburg, Gothenburg, Sweden
  • Boi, Roberto, University of Gothenburg, Gothenburg, Sweden
  • Wallentin, Hanna Ilse, University of Gothenburg, Gothenburg, Sweden
  • Haraldsson, Borje, Novartis, Gothenburg, Switzerland
  • Nystrom, Jenny C., University of Gothenburg, Gothenburg, Sweden
  • Buvall, Lisa, University of Gothenburg, Gothenburg, Sweden

The Melanocortin-1 receptor in podocytes has been suggested as the mediator of the renoprotective effects seen in ACTH treatment of nephrotic syndrome. The protective effect has been proposed to be through stabilization of the actin cytoskeleton in podocytes.


Using phosphoproteomic mass spectrometry, actin regulatory pathways were identified downstream of the MC1R in podocytes over-expressing the MC1R and treated with the MC1R specific agonist BMS. Confirmation of regulated proteins and pathways was done using western blot. Actin dynamics was studied using phalloidin labeling. To evaluate the protective effect of MC1R-induced ERK phosphorylation and EGFR signaling, protamine sulfate was used on cultured podocytes in the presence or absence of the ERK-inhibitor PD98059.


Actin cytoskeleton signaling was the toped ranked regulated pathway in podocytes identified in the phosphoproteomic data following BMS treatment. The activity of MAP-kinases, ERK and the EGFR was found to be significantly regulated. To confirm the proteomics data, western blot analysis was performed. Increased phosphorylation of ERK1/2 following BMS treatment was observed already after 5 minutes. This was followed by an increase in phosphorylation on EGFR T669, a site commonly phosphorylated by ERK and known to inactivate the receptor. Perturbed EGFR signaling was observed in MC1R activated podocytes shown by increased downregulation of the EGFR following EGF treatment in BMS exposed cells. MC1R was shown to protect podocytes from protamine sulfate induced EGFR activation and actin cytoskeleton rearrangement in podocytes. The rescue effect was shown to be attenuated by inhibiting ERK.


In this study, we show that MC1R activation leads to the ERK-dependent phosphorylation of EGFR T669, with ensuing downregulation of the receptor. Activation of the EGFR has previously been shown to be a negative regulator of actin cytoskeleton dynamics in podocytes. These data thereby suggest that the MC1R protective effect on the actin cytoskeleton in podocytes is due to its inhibitory role on EGFR signaling.


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