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

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...

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Autores principales: Casili, Giovanna, Scuderi, Sarah Adriana, Lanza, Marika, Filippone, Alessia, Basilotta, Rossella, Mannino, Deborah, Campolo, Michela, Esposito, Emanuela, Paterniti, Irene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378771/
https://www.ncbi.nlm.nih.gov/pubmed/34434495
http://dx.doi.org/10.18632/oncotarget.28041
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author Casili, Giovanna
Scuderi, Sarah Adriana
Lanza, Marika
Filippone, Alessia
Basilotta, Rossella
Mannino, Deborah
Campolo, Michela
Esposito, Emanuela
Paterniti, Irene
author_facet Casili, Giovanna
Scuderi, Sarah Adriana
Lanza, Marika
Filippone, Alessia
Basilotta, Rossella
Mannino, Deborah
Campolo, Michela
Esposito, Emanuela
Paterniti, Irene
author_sort Casili, Giovanna
collection PubMed
description 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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spelling pubmed-83787712021-08-24 The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion Casili, Giovanna Scuderi, Sarah Adriana Lanza, Marika Filippone, Alessia Basilotta, Rossella Mannino, Deborah Campolo, Michela Esposito, Emanuela Paterniti, Irene Oncotarget Research Paper 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. Impact Journals LLC 2021-08-17 /pmc/articles/PMC8378771/ /pubmed/34434495 http://dx.doi.org/10.18632/oncotarget.28041 Text en Copyright: © 2021 Casili et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Casili, Giovanna
Scuderi, Sarah Adriana
Lanza, Marika
Filippone, Alessia
Basilotta, Rossella
Mannino, Deborah
Campolo, Michela
Esposito, Emanuela
Paterniti, Irene
The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title_full The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title_fullStr The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title_full_unstemmed The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title_short The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
title_sort protective role of prolyl oligopeptidase (pop) inhibition in acute lung injury induced by intestinal ischemia-reperfusion
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378771/
https://www.ncbi.nlm.nih.gov/pubmed/34434495
http://dx.doi.org/10.18632/oncotarget.28041
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