Ssian Science Foundation, grant no. 21-14-00381. Institutional Assessment Board Statement: Not applicable. Informed Consent Statement:

Ssian Science Foundation, grant no. 21-14-00381. Institutional Assessment Board Statement: Not applicable. Informed Consent Statement: Not applicable.Int. J. Mol. Sci. 2021, 22,19 ofData Lapatinib-d5 Protocol Availability Statement: This can be a overview paper that collected from public data listed in the Reference section. Conflicts of Interest: The authors declare no conflict of interest.International Journal ofMolecular SciencesArticleThe Protective Function of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia eperfusionGiovanna Casili, Alessio Ardizzone, Rossella Basilotta, Marika Lanza, Alessia Filippone, Irene Paterniti, Emanuela Esposito and Michela CampoloDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31-98166 Messina, Italy; [email protected] (G.C.); [email protected] (A.A.); rossella.basilotta@gmail (R.B.); [email protected] (M.L.); [email protected] (A.F.); [email protected] (I.P.); [email protected] (M.C.) Correspondence: [email protected]; Tel.: 39-090-Citation: Casili, G.; Ardizzone, A.; Basilotta, R.; Lanza, M.; Filippone, A.; Paterniti, I.; Esposito, E.; Campolo, M. The Protective Function of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia eperfusion. Int. J. Mol. Sci. 2021, 22, 11886. ten.3390/ijms222111886 Academic Editors: Andreas Kronbichler and Vladimir Tesar Received: 29 September 2021 Accepted: 28 October 2021 Published: 2 NovemberAbstract: Ischemia/reperfusion injury (IRI) is often a complex pathophysiological approach characterized by blood circulation disorder caused by different components, which include traumatic shock, surgery, organ transplantation, and thrombus. Extreme metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow towards the ischemic tissue. The kidney is really a extremely perfused organ, sensitive to ischemia and reperfusion injury, and also the Florfenicol-d3 Purity incidence of renal IRI has high morbidity and mortality. Several research showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Regardless of advances in research, helpful 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 analysis focused on the part of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice had been subjected to KYP2047 therapy (intraperitoneal, 0.5, 1 and five 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 had been performed on kidney samples. In addition, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and five mg/kg, considerably lowered renal injury and collagen quantity, regulated inflammation via canonical and non-canonical NF-B pathway, and restored renal function. Additionally, KYP2047 modulated angiogenesis markers, like TGF- and VEGF, also slowing down apoptosis. Interestingly, remedy with KYP2047 modulated PP2A activity. Thus, these findings clarified the function of POP inhibition in AKI, also offering novel therapeutic target for renal injury following KI/R. Keywords: kidney ischemia reperfusion (KI/R); acute kidney injury (AKI); prolyl oligopept.