The fibrin cleavage product Bβ15–42 channels endothelial and tubular regeneration in the post-acute course during murine renal ischemia reperfusion injury

  • Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bβ15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin. Therefore, this study focused on the effect of Bβ15-42 on post-acute physiological renal regeneration. For this, adult male C57BL/6 mice were exposed to a 30 min bilateral renal ischemia and reperfusion for 24 h or 48 h. Animals were randomized in a non-operative control group, two operative groups each treated with i.v. administration of either saline or Bβ15-42 (2.4 mg/kg) immediately prior to reperfusion. Endothelial activation and inflammatory response was attenuated in renal tissue homogenates by single application of Bβ15-42. Meanwhile, Bβ15-42 did not affect acute kidney injury markers. Regarding the angiogenetic players VEGF-A, Angiopoietin-1, Angiopoietin-2, however, we observed significant higher expressions at mRNA and trend to higher protein level in Bβ15-42 treated mice, compared to saline treated mice after 48 h of IR, thus pointing toward an increased angiogenetic activity. Similar dynamics were observed for the intermediate filament vimentin, the cytoprotective protein klotho, stathmin and the proliferation cellular nuclear antigen, which were significantly up-regulated at the same points in time. These results suggest a beneficial effect of anatomical contiguously located endothelial cells on tubular regeneration through stabilization of endothelial integrity. Therefore, it seems that Bβ15-42 represents a novel pharmacological approach in the targeted therapy of acute renal failure in everyday clinical practice.

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Author:Dania Fischer, Christopher Seifen, Patrick BaerORCiDGND, Michaela JungORCiD, Christina Mertens, Bertram Scheller, Kai ZacharowskiORCiDGND, Rainer Hofmann, Thorsten Jürgen Maier, Anja Urbschat
URN:urn:nbn:de:hebis:30:3-466901
DOI:https://doi.org/10.3389/fphar.2018.00369
ISSN:1663-9812
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29755348
Parent Title (English):Frontiers in pharmacology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Orina Belton
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/04/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/06/19
Tag:FX06; angiogenesis; endothelial activation; primary mouse proximal tubular cells; renal ischemia reperfusion injury; tubular regeneration
Volume:9
Issue:Art. 369
Page Number:13
First Page:1
Last Page:13
Note:
Copyright © 2018 Fischer, Seifen, Baer, Jung, Mertens, Scheller, Zacharowski, Hofmann, Maier and Urbschat. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS-PPN:434437085
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0