TRANSLATIONAL IMPLICATIONS OF ENDOTHELIAL CELL DYSFUNCTION IN ASSOCIATION WITH CHRONIC ALLOGRAFT REJECTION

Upon binding to graft microvascular endothelial cells (EC), leukocytes, inflammatory cytokines, growth factors (incl. VEGF, ) and alloantibodies activate PI3K/Akt/mTOR-mediated signals. Assembly of mTORC2 complex results in the phosphorylation and activation of the Akt kinase, that in turn activates mTORC1 and its substrates 4EBP1 and S6K1. Collectively, these signals result in EC activation, migration and proliferation. In addition, Akt-mediated signals enhance the activity of ERK1/2, which also promotes EC activation. The endogenous protein DEPTOR inhibits mTORC1 and ERK1/2, as well as STAT-1 signaling in EC, highlighting its major function as a cell-intrinsic regulatory of EC activation responses. Several miRNAs have been found to control the activity of the mTOR pathway as well as endothelial cell activation. Notably, endothelial specific miR-126 functions to inactivate both PI3K/Akt- and ERK1/2-mediated signals and thus maintain EC quiescence.

Publication

TRANSLATIONAL IMPLICATIONS OF ENDOTHELIAL CELL DYSFUNCTION IN ASSOCIATION WITH CHRONIC ALLOGRAFT REJECTION. () Sarah Bruneau, et al. Pediatr Nephrol. ;31(1):41-51. Figure: F2. All organisms Danio rerio Homo sapiens

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