Abstract: TH-PO354

Extracellular YB-1, as Signal of Tissue Damage, Induces Mesangial Cell Migration and Proliferation

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress


  • Brandt, Sabine, Otto-von-Guericke University, Magdeburg, Germany
  • Scurt, Florian Gunnar, Otto-von-Guericke University, Magdeburg, Germany
  • Lindquist, Jonathan A, Otto-von-Guericke University, Magdeburg, Germany
  • Mertens, Peter R., Otto-von-Guericke University, Magdeburg, Germany

The Y-box protein-1 (YB-1) is the prototypic member of the cold shock protein family of RNA/DNA binding proteins. Recent findings indicate acetylation-dependent secretion of YB-1 via a non-classical pathway and profound extracellular effects mediated by Notch-3 receptors.


Here we determined changes in gene expression and proliferation in rat mesangial cells following stimulation with recombinant YB-1, truncated YB-1, and peptides corresponding to domains of YB-1.


Stimulation of mesangial cells with recombinant YB-1 resulted in an up-regulation of defined target genes and surprisingly even YB-1 itself. Further analysis revealed that recombinant YB-1 is capable of enhancing proliferation and migration rates. We also confirmed the chemokine activity using human peripheral blood mononuclear cells in a Boyden chamber assay. YB-1 significantly increases the specific migration of cells compared to the basal rate. Additionally, subcutaneous injection of recombinant YB-1 induced immune cell infiltration. Furthermore activation of monocytes with pro-inflammatory stimuli induces the secretion of YB-1.


Taken together, our results indicate a feed-forward loop with activation of signaling cascades by extracellular YB-1 that results in the phosphorylation of Akt, MAPK/ERK, and STAT proteins, up-regulation of YB-1 expression and target gene regulation, as well as an increase in cell proliferation and migration. Thus, we identify extracellular YB-1 as potent extracellular mediator of cell activation in inflammatory diseases.


  • Government Support - Non-U.S.