The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion

The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion

Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon re...

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Autores principales: Giovanna Casili, Alessio Ardizzone, Rossella Basilotta, Marika Lanza, Alessia Filippone, Irene Paterniti, Emanuela Esposito, Michela Campolo
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
kidney ischemia reperfusion (KI/R)
acute kidney injury (AKI)
prolyl oligopeptidase (POP)
inflammation
apoptosis
angiogenesis
Biology (General)
QH301-705.5
Chemistry
QD1-999
Acceso en línea:https://doaj.org/article/7a0174a53a5b45b984774e73e37047c4
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spelling oai:doaj.org-article:7a0174a53a5b45b984774e73e37047c42021-11-11T17:19:20ZThe Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion10.3390/ijms2221118861422-00671661-6596https://doaj.org/article/7a0174a53a5b45b984774e73e37047c42021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11886https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.Giovanna CasiliAlessio ArdizzoneRossella BasilottaMarika LanzaAlessia FilipponeIrene PaternitiEmanuela EspositoMichela CampoloMDPI AGarticlekidney ischemia reperfusion (KI/R)acute kidney injury (AKI)prolyl oligopeptidase (POP)inflammationapoptosisangiogenesisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11886, p 11886 (2021)
institution DOAJ
collection DOAJ
language EN
topic kidney ischemia reperfusion (KI/R)
acute kidney injury (AKI)
prolyl oligopeptidase (POP)
inflammation
apoptosis
angiogenesis
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle kidney ischemia reperfusion (KI/R)
acute kidney injury (AKI)
prolyl oligopeptidase (POP)
inflammation
apoptosis
angiogenesis
Biology (General)
QH301-705.5
Chemistry
QD1-999
Giovanna Casili
Alessio Ardizzone
Rossella Basilotta
Marika Lanza
Alessia Filippone
Irene Paterniti
Emanuela Esposito
Michela Campolo
The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
description Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.
format article
author Giovanna Casili
Alessio Ardizzone
Rossella Basilotta
Marika Lanza
Alessia Filippone
Irene Paterniti
Emanuela Esposito
Michela Campolo
author_facet Giovanna Casili
Alessio Ardizzone
Rossella Basilotta
Marika Lanza
Alessia Filippone
Irene Paterniti
Emanuela Esposito
Michela Campolo
author_sort Giovanna Casili
title The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
title_short The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
title_full The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
title_fullStr The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
title_full_unstemmed The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
title_sort protective role of prolyl oligopeptidase (pop) inhibition in kidney injury induced by renal ischemia–reperfusion
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/7a0174a53a5b45b984774e73e37047c4
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