{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:34:46Z","timestamp":1790451286621,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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-\u03baB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-\u03b2 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.<\/jats:p>","DOI":"10.3390\/ijms222111886","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T22:17:23Z","timestamp":1635891443000},"page":"11886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia\u2013Reperfusion"],"prefix":"10.3390","volume":"22","author":[{"given":"Giovanna","family":"Casili","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-0634","authenticated-orcid":false,"given":"Alessio","family":"Ardizzone","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Basilotta","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Lanza","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Filippone","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Paterniti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Campolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres, 31-98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/TA.0b013e31829de6cd","article-title":"Acute kidney injury is surprisingly common and a powerful predictor of mortality in surgical sepsis","volume":"75","author":"White","year":"2013","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1611391","article-title":"Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults","volume":"376","author":"Kaddourah","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nieuwenhuijs-Moeke, G.J., Pischke, S.E., Berger, S.P., Sanders, J.S.F., Pol, R.A., Struys, M., Ploeg, R.J., and Leuvenink, H.G.D. (2020). Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010253"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrneph.2011.16","article-title":"Pathophysiology of ischemic acute kidney injury","volume":"7","author":"Sharfuddin","year":"2011","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1681\/ASN.2015070740","article-title":"Cellular and Molecular Mechanisms of AKI","volume":"27","author":"Agarwal","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_6","first-page":"2001","article-title":"Acute kidney injury","volume":"2011","author":"Kellum","year":"2011","journal-title":"BMJ Clin. Evid."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2180373","DOI":"10.1155\/2018\/2180373","article-title":"Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome","volume":"2018","author":"Mihai","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/intimm\/dxq025","article-title":"Chemokine expression in renal ischemia\/reperfusion injury is most profound during the reparative phase","volume":"22","author":"Stroo","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.febslet.2011.12.022","article-title":"Double-stranded RNA induces S100 gene expression by a cycloheximide-sensitive factor","volume":"586","author":"Voss","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/00041552-200205000-00006","article-title":"Role of apoptosis in the pathogenesis of acute renal failure","volume":"11","author":"Bonegio","year":"2002","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/S1166-7087(14)70059-4","article-title":"Angiogenic response following renal ischemia reperfusion injury: New players","volume":"24","author":"Pallet","year":"2014","journal-title":"Prog. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/sj.ki.5002312","article-title":"The endothelial cell in ischemic acute kidney injury: Implications for acute and chronic function","volume":"72","author":"Basile","year":"2007","journal-title":"Kidney Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1177\/1535370216684040","article-title":"Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort","volume":"242","author":"Wolke","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00418-008-0468-x","article-title":"Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues","volume":"130","author":"Myohanen","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1159\/000142934","article-title":"Inflammation in acute kidney injury","volume":"109","author":"Kinsey","year":"2008","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/187152711794653742","article-title":"Prolyl oligopeptidase: A rising star on the stage of neuroinflammation research","volume":"10","author":"Penttinen","year":"2011","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S318","DOI":"10.1042\/bst026s318","article-title":"Inhibitors of poly (ADP-ribose) synthetase protect rat renal proximal tubular cells against oxidant stress","volume":"26","author":"Chatterjee","year":"1998","journal-title":"Biochem. Soc. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/08860220802546487","article-title":"Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: A histopathologic study","volume":"31","author":"Kocoglu","year":"2009","journal-title":"Ren. Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.biochi.2012.04.005","article-title":"Four day inhibition of prolyl oligopeptidase causes significant changes in the peptidome of rat brain, liver and kidney","volume":"94","author":"Mannisto","year":"2012","journal-title":"Biochimie"},{"key":"ref_20","first-page":"17","article-title":"Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids","volume":"34","author":"Goossens","year":"1996","journal-title":"Eur. J. Clin. Chem. Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9353","DOI":"10.1038\/s41598-018-27107-8","article-title":"Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease","volume":"8","author":"Bouman","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1681\/ASN.2010080796","article-title":"Biological markers of acute kidney injury","volume":"22","author":"Siew","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1159\/000313725","article-title":"Oliguria, creatinine and other biomarkers of acute kidney injury","volume":"164","author":"Ronco","year":"2010","journal-title":"Contrib. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ki.2011.379","article-title":"Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis","volume":"81","author":"Coca","year":"2012","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nrneph.2015.3","article-title":"Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD","volume":"11","author":"Ferenbach","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000363705","article-title":"Cardiac and renal fibrosis in chronic cardiorenal syndromes","volume":"127","author":"Hundae","year":"2014","journal-title":"Nephron Clin. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s40472-014-0017-6","article-title":"Ischemia\/reperfusion Injury and its Consequences on Immunity and Inflammation","volume":"1","author":"Slegtenhorst","year":"2014","journal-title":"Curr. Transpl. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cca.2006.09.001","article-title":"Suggested functions for prolyl oligopeptidase: A puzzling paradox","volume":"377","author":"Brandt","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1126\/science.1071914","article-title":"The IkappaB-NF-kappaB signaling module: Temporal control and selective gene activation","volume":"298","author":"Hoffmann","year":"2002","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1097-2765(01)00187-3","article-title":"NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100","volume":"7","author":"Xiao","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.freeradbiomed.2005.03.028","article-title":"Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: A systematic review","volume":"39","author":"Willmot","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R693","DOI":"10.1152\/ajpregu.00422.2013","article-title":"Combined therapy with COX-2 inhibitor and 20-HETE inhibitor reduces colon tumor growth and the adverse effects of ischemic stroke associated with COX-2 inhibition","volume":"307","author":"Zhang","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.4049\/jimmunol.1601282","article-title":"Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury","volume":"198","author":"Danelli","year":"2017","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1161\/01.CIR.98.7.699","article-title":"Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia\/reperfusion","volume":"98","author":"Frangogiannis","year":"1998","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/S1166-7087(14)70057-0","article-title":"Ischemia-reperfusion: From cell biology to acute kidney injury","volume":"24","author":"Chatauret","year":"2014","journal-title":"Prog. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/35025220","article-title":"Angiogenesis in cancer and other diseases","volume":"407","author":"Carmeliet","year":"2000","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0140-6736(05)70238-5","article-title":"Acute renal failure","volume":"365","author":"Lameire","year":"2005","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.semnephrol.2016.04.001","article-title":"The Role of BCL-2 Family Members in Acute Kidney Injury","volume":"36","author":"Borkan","year":"2016","journal-title":"Semin. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104558","DOI":"10.1016\/j.phrs.2019.104558","article-title":"Prolyl oligopeptidase inhibition activates autophagy via protein phosphatase 2A","volume":"151","author":"Svarcbahs","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9634","DOI":"10.1111\/jcmm.16910","article-title":"Prolyl oligopeptidase inhibition reduces alpha-synuclein aggregation in a cellular model of multiple system atrophy","volume":"25","author":"Cui","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3892\/etm.2021.10671","article-title":"Role of protein phosphatase 2A in kidney disease (Review)","volume":"22","author":"Shao","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/MCC.0b013e328332f6cf","article-title":"The role of the microcirculation in acute kidney injury","volume":"15","author":"Legrand","year":"2009","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/sj.ki.5002297","article-title":"Community-based incidence of acute renal failure","volume":"72","author":"Hsu","year":"2007","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1053\/j.ajkd.2008.11.034","article-title":"Long-term risk of mortality and other adverse outcomes after acute kidney injury: A systematic review and meta-analysis","volume":"53","author":"Coca","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1172\/JCI72269","article-title":"Therapeutic translation in acute kidney injury: The epithelial\/endothelial axis","volume":"124","author":"Molitoris","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Casili, G., Lanza, M., Scuderi, S.A., Messina, S., Paterniti, I., Campolo, M., and Esposito, E. (2020). The Inhibition of Prolyl Oligopeptidase as New Target to Counteract Chronic Venous Insufficiency: Findings in a Mouse Model. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120604"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"983","DOI":"10.21037\/atm-20-3412","article-title":"The role of prolyl oligopeptidase, understanding the puzzle","volume":"8","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1248\/bpb1978.10.730","article-title":"Specific inhibitors for prolyl endopeptidase and their anti-amnesic effect","volume":"10","author":"Yoshimoto","year":"1987","journal-title":"J. Pharmacobiodyn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0304-3940(95)11821-D","article-title":"Increase in the septal vasopressin content by prolyl endopeptidase inhibitors in rats","volume":"196","author":"Miura","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0092-8674(00)81416-6","article-title":"Prolyl oligopeptidase: An unusual beta-propeller domain regulates proteolysis","volume":"94","author":"Fulop","year":"1998","journal-title":"Cell"},{"key":"ref_52","first-page":"23","article-title":"Regulation of kidney function and metabolism: A question of supply and demand","volume":"118","author":"Blantz","year":"2007","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_53","first-page":"153","article-title":"Acute Kidney Injury: Diagnostic Approaches and Controversies","volume":"37","author":"Makris","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13054-015-0805-0","article-title":"Long-term sequelae from acute kidney injury: Potential mechanisms for the observed poor renal outcomes","volume":"19","author":"Varrier","year":"2015","journal-title":"Crit. Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mam.2018.06.002","article-title":"Cellular and molecular mechanisms of kidney fibrosis","volume":"65","author":"Djudjaj","year":"2019","journal-title":"Mol. Aspects Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1046\/j.1440-1711.2001.01004.x","article-title":"Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1","volume":"79","author":"Umehara","year":"2001","journal-title":"Immunol. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"F928","DOI":"10.1152\/ajprenal.00596.2007","article-title":"Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor","volume":"294","author":"Basile","year":"2008","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s10020-019-0072-7","article-title":"Angiopoietin 1 influences ischemic reperfusion renal injury via modulating endothelium survival and regeneration","volume":"25","author":"Chiang","year":"2019","journal-title":"Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/jcp.21706","article-title":"Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis","volume":"219","author":"Ferrari","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fcell.2020.00123","article-title":"Diverse Role of TGF-beta in Kidney Disease","volume":"8","author":"Gu","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.clim.2006.09.008","article-title":"Triggers of inflammation after renal ischemia\/reperfusion","volume":"123","author":"Thurman","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrneph.2014.114","article-title":"Inflammatory processes in renal fibrosis","volume":"10","author":"Meng","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000081558","article-title":"Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin","volume":"98","author":"Volpini","year":"2004","journal-title":"Nephron Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00011-014-0763-z","article-title":"The role of mast cells in ischemia and reperfusion injury","volume":"63","author":"Yang","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1523-1755.2005.00200.x","article-title":"IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia\u2014The good, the bad, and the ugly","volume":"67","author":"Stenvinkel","year":"2005","journal-title":"Kidney Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1681\/ASN.V1081737","article-title":"Developmental expression of protein phosphatase 2A in the kidney","volume":"10","author":"Everett","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"F1073","DOI":"10.1152\/ajprenal.00354.2020","article-title":"AMP-activated protein kinase contributes to cisplatin-induced renal epithelial cell apoptosis and acute kidney injury","volume":"319","author":"Jin","year":"2020","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ejphar.2012.11.066","article-title":"The renal injury and inflammation caused by ischemia-reperfusion are reduced by genetic inhibition of TNF-alphaR1: A comparison with infliximab treatment","volume":"700","author":"Genovese","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Le Clef, N., Verhulst, A., D\u2019Haese, P.C., and Vervaet, B.A. (2016). Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152153"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1124\/mol.66.2.220","article-title":"Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton","volume":"66","author":"Patel","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Campolo, M., Siracusa, R., Cordaro, M., Filippone, A., Gugliandolo, E., Peritore, A.F., Impellizzeri, D., Crupi, R., Paterniti, I., and Cuzzocrea, S. (2019). The association of adelmidrol with sodium hyaluronate displays beneficial properties against bladder changes following spinal cord injury in mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0208730"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.aju.2012.08.003","article-title":"Protection against renal ischaemia\/reperfusion injury: A comparative experimental study of the effect of ischaemic preconditioning vs. postconditioning","volume":"10","author":"Shokeir","year":"2012","journal-title":"Arab. J. Urol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Casili, G., Ardizzone, A., Lanza, M., Gugliandolo, E., Portelli, M., Militi, A., Cuzzocrea, S., Esposito, E., and Paterniti, I. (2020). Treatment with Luteolin Improves Lipopolysaccharide-Induced Periodontal Diseases in Rats. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100442"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.18632\/oncotarget.28041","article-title":"The protective role of prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion","volume":"12","author":"Casili","year":"2021","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Loganathan, K., Salem Said, E., Winterrowd, E., Orebrand, M., He, L., Vanlandewijck, M., Betsholtz, C., Quaggin, S.E., and Jeansson, M. (2018). Angiopoietin-1 deficiency increases renal capillary rarefaction and tubulointerstitial fibrosis in mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0189433"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Scuderi, S.A., Casili, G., Ardizzone, A., Forte, S., Colarossi, L., Sava, S., Paterniti, I., Esposito, E., Cuzzocrea, S., and Campolo, M. (2021). KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces GlioBlastoma Proliferation through Angiogenesis and Apoptosis Modulation. Cancers, 13.","DOI":"10.3390\/cancers13143444"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1089\/neu.2017.5260","article-title":"Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits Induced by Experimental Traumatic Brain Injury","volume":"35","author":"Casili","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1007\/s12035-018-1347-7","article-title":"Sodium Butyrate Exerts Neuroprotective Effects in Spinal Cord Injury","volume":"56","author":"Lanza","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1007\/s12035-020-02033-x","article-title":"Role of ABT888, a Novel Poly(ADP-Ribose) Polymerase (PARP) Inhibitor in Countering Autophagy and Apoptotic Processes Associated to Spinal Cord Injury","volume":"57","author":"Casili","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"106825","DOI":"10.1016\/j.vph.2020.106825","article-title":"Therapeutic potential of flavonoids in the treatment of chronic venous insufficiency","volume":"137","author":"Casili","year":"2021","journal-title":"Vascul. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"69","DOI":"10.15171\/jnp.2017.12","article-title":"Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in rats subjected to hemorrhagic shock","volume":"6","author":"Ranjbaran","year":"2017","journal-title":"J. Nephropathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:54Z","timestamp":1760167494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,2]]},"references-count":81,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111886"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111886","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,2]]}}}