Oncotarget

Research Papers:

The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion

Giovanna Casili, Sarah Adriana Scuderi, Marika Lanza, Alessia Filippone, Rossella Basilotta, Deborah Mannino, Michela Campolo, Emanuela Esposito and Irene Paterniti _

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Oncotarget. 2021; 12:1663-1676. https://doi.org/10.18632/oncotarget.28041

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Abstract

Giovanna Casili1, Sarah Adriana Scuderi1, Marika Lanza1, Alessia Filippone1, Rossella Basilotta1, Deborah Mannino1, Michela Campolo1, Emanuela Esposito1 and Irene Paterniti1

1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy

Correspondence to:

Irene Paterniti, email: ipaterniti@unime.it

Keywords: intestinal ischemia reperfusion (II/R); acute lung injury (ALI); prolyl oligopeptidase (POP); inflammation; angiogenesis

Received: May 25, 2021     Accepted: July 27, 2021     Published: August 17, 2021

Copyright: © 2021 Casili et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Intestinal ischemia-reperfusion (II/R) develops when the blood flow to the intestines decreases, followed by the reestablishment of the blood supply to the ischemic tissue, resulting in intestinal mucosal barrier dysfunction, with consequent severe local and systemic inflammation. Acute lung injury (ALI) represents the most serious complication after II/R. KYP-2047 is a selective inhibitor of prolyl oligopeptidase (POP), a serine protease involved in the release of pro-angiogenic and inflammatory molecules. The aim of the present study is to assess the effects of POP-inhibition mediated by KYP-2047 treatment in the pathophysiology of ALI following II/R. An in vivo model of II/R was performed and mice were subjected to KYP-2047 treatment (intraperitoneal, 1, 2.5 and 5 mg/kg). Histological analysis, Masson’s trichrome staining, immunohistochemical, immunofluorescence, biochemical and western blots analysis were performed on ileum and lung samples. KYP-2047 treatment ameliorated histological alteration in ileum and lung, reduced collagen amount and lowered inflammatory protein levels. Moreover, TGF-β1, eNOS, VEGF and CD34 positive staining has been modulated; also, a reduction in apoptosis expression was confirmed. This research revealed the strong anti-inflammatory potential of KYP-2047 associated to its modulatory role on angiogenesis and apoptosis, suggesting POP as a novel therapeutic target for ALI after II/R.


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