Modulation of proteomic and inflammatory signals by Bradykinin in podocytes

Richard Saoud, Miran A. Jaffa, Aida Habib, Jingfu Zhao, Moustafa Al Hariri, Rui Zhu, Anwarul Hasan, Fuad N. Ziyadeh, Firas Kobeissy, Yehia Mechref, Ayad A. Jaffa

Research output: Contribution to journalArticlepeer-review

Abstract

Podocyte damage is one of the hallmarks of diabetic nephropathy leading to proteinuria and kidney damage. The underlying mechanisms of podocyte injury are not well defined. Bradykinin (BK) was shown to contribute to diabetic kidney disease. Here, we evaluated the temporal changes in proteome profile and inflammatory signals of podocytes in response to BK (10−7M). Protein profile was evaluated by liquid chromatography mass Spectrometry (LC-MS/MS) analysis. Proteome profile analysis of podocytes treated with BK (10−7M) for 3 and 6 h, revealed 61 proteins that were differentially altered compared to unstimulated control podocytes. Pathway enrichment analysis suggested inhibition of cell death pathways, engagement of cytoskeletal elements and activation of inflammatory pathways. One of the inflammatory proteins that was identified to be induced by BK treatment is Prostaglandin (PG) H Synthase-2 (Cyclooxygenase-2, COX-2). In addition, BK significantly induced the production and release of PGE2 and this effect was inhibited by both COX-2 and MEK Kinase inhibitors, demonstrating that the production of PGE2 by BK is mediated via COX-2 and MAPK-dependent mechanisms. These findings provide a global understanding of the effector modulated proteome in response to BK and also reveal BK as an important modulator of inflammation and a potential player in podocyte injury.

Original languageEnglish
Pages (from-to)409-422
Number of pages14
JournalJournal of Advanced Research
Volume24
DOIs
StatePublished - Jul 2020

Keywords

  • Bradykinin 2 receptor
  • Cyclooxygenase-2
  • ERK1/2
  • Liquid Chromatography Mass Spectrometry
  • Podocyte proteome

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