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. 2022 Jun 15;11(12):1935. doi: 10.3390/cells11121935

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Targeting procalcitonin protects vascular barrier integrity during hyperprocalcitonemia in systemic inflammation. Dipeptidyl peptidase 4 (DPP4) mediates N-terminal truncation of full-length 116-amino-acid-long procalcitonin into its truncated bioactive 114-amino-acid-containing variant. The truncated form binds to CRLR/RAMP1 complex on endothelial cells, which induces phosphorylation of VE-cadherin leading to disruption of VE-cadherin assembly and thus, to vascular leakage induction. As shown in the present figure, antagonizing procalcitonin actions via DPP4 inhibition by sitagliptin and via CRLR/RAMP1 blockage by olcegepant specifically preserves endothelial barrier integrity in murine polymicrobial sepsis. This figure was created with BioRender.com.