• Inga Sörensen-Zender, Rongjun Chen, Song Rong, Sascha David, Anette Melk, Hermann Haller, and Roland Schmitt.
• Department of Nephrology and Hypertension, Medical School Hannover, Germany. Electronic address: soerensen.inga@mh-hannover.de.
• Transl Res. 2019 Nov 1; 213: 124-135.

AbstractDuring 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.Copyright © 2019 Elsevier Inc. All rights reserved.

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