Research Article| Volume 213, P124-135, November 2019

Binding to carboxypeptidase M mediates protective effects of fibrinopeptide Bβ15-42

      During fibrinolysis a 28-amino-acid peptide is generated besides other degradation products of fibrin. This peptide, called Bβ15–42, which is cleaved by plasmin from the end of the fibrin Bβ-chain, is protective in myocardial and renal ischemia/reperfusion injury and improves the outcome in experimental sepsis. Bβ15–42 has been shown to mediate different beneficial effects in endothelial cells through binding to vascular endothelial-cadherin. Here, we provide in vitro and in vivo evidence that Bβ15–42 has additional cell protective activity in tubular cells, which is caused by a distinct mechanism. As vascular endothelial-cadherin is not expressed by tubular cells we used ligand-receptor capture technology LRC-TriCEPS to search for tubular cell surface receptors and identified carboxypeptidase M (CBPM) as a novel binding partner of Bβ15–42. Silencing CBPM with siRNA reduced the protective potential of Bβ15–42 against tubular cell stress. Bβ15–42 inhibited the enzymatic activity of CBPM and modified the impact of CBPM on bradykinin signaling. We conclude that beneficial properties of Bβ15–42 are not restricted to endothelial cells but are also active in epithelial cells where cytoprotection depends on CBPM binding.


      AA (Aristolochic Acid), AAN (Aristolochic Acid induced Nephropathy), BK (Bradykinin), BR-1 (Bradykinin Receptor B1), BR-2 (Bradykinin Receptor B2), CBPM (Carboxypeptidase M), Ctrl (Control), DMSO (Dimethyl Sulfoxide), I/R (Ischemia/Reperfusion), LDH (Lactate Dehydrogenase), LRC (Ligand-based Receptor Capturing), NGAL (Neutrophil gelatinase-associated lipocalin), PCR (Polymerase Chain Reaction), PFA (Paraformaldehyde), UUO (Unilateral Ureteral Obstruction), VE-cadherin (Vascular Endothelial cadherin), VLDLR (Very Low Density Lipoprotein Receptor)
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