{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:47:36Z","timestamp":1792180056955,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1D1A1B03036316"],"award-info":[{"award-number":["NRF-2017R1D1A1B03036316"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1F1A1061445"],"award-info":[{"award-number":["NRF-2021R1F1A1061445"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and progression to chronic kidney disease (CKD). However, no effective therapeutic intervention has been established for ischemic AKI. Endothelial progenitor cells (EPCs) have major roles in the maintenance of vascular integrity and the repair of endothelial damage; they also serve as therapeutic agents in various kidney diseases. Thus, we examined whether EPCs have a renoprotective effect in an IRI mouse model. Mice were assigned to sham, EPC, IRI-only, and EPC-treated IRI groups. EPCs originating from human peripheral blood were cultured. The EPCs were administered 5 min before reperfusion, and all mice were killed 72 h after IRI. Blood urea nitrogen, serum creatinine, and tissue injury were significantly increased in IRI mice; EPCs significantly improved the manifestations of IRI. Apoptotic cell death and oxidative stress were significantly reduced in EPC-treated IRI mice. Administration of EPCs decreased the expression levels of NLRP3, cleaved caspase-1, p-NF-\u03baB, and p-p38. Furthermore, the expression levels of F4\/80, ICAM-1, ROR\u03b3t, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-\u03b2, \u03b1-SMA, Snail, and Twist) were significantly reduced in EPC-treated IRI mice. This study shows that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target of EPCs as a treatment for IRI-induced AKI and the prevention of progression to CKD.<\/jats:p>","DOI":"10.3390\/ijms23031546","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"1546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Ha Nee","family":"Jang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-6481","authenticated-orcid":false,"given":"Jin Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong Hee","family":"Jung","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekil","family":"Tak","sequence":"additional","affiliation":[{"name":"Gyeongnam Biohealth Research Center, Korea Institute of Toxicology, Jinju 52834, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-8262","authenticated-orcid":false,"given":"Jung Hwa","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"},{"name":"Division of Endocrinology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghye","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehyun","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Ho","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5883-4735","authenticated-orcid":false,"given":"Hyun-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea"},{"name":"Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1159\/000337487","article-title":"Acute kidney injury and mortality in hospitalized patients","volume":"35","author":"Wang","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s00134-021-06454-7","article-title":"Acute kidney injury in the critically ill: An updated review on pathophysiology and management","volume":"47","author":"Pickkers","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/cphy.c110041","article-title":"Pathophysiology of acute kidney injury","volume":"2","author":"Basile","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1177\/0004563214556820","article-title":"Pathophysiology of ischaemic acute kidney injury","volume":"52","author":"Kanagasundaram","year":"2015","journal-title":"Ann. Clin. Biochem."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41581-019-0158-z","article-title":"The role of inflammasomes in kidney disease","volume":"15","author":"Komada","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1681\/ASN.2010080798","article-title":"The inflammasomes in kidney disease","volume":"22","author":"Anders","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1161\/01.RES.0000137877.89448.78","article-title":"Endothelial progenitor cells: Characterization and role in vascular biology","volume":"95","author":"Urbich","year":"2004","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1159\/000489745","article-title":"Endothelial Progenitor Cells and Kidney Diseases","volume":"43","author":"Ozkok","year":"2018","journal-title":"Kidney Blood Press Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1159\/000202005","article-title":"The role of endothelial progenitor cells in acute kidney injury","volume":"27","author":"Becherucci","year":"2009","journal-title":"Blood Purif."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F679","DOI":"10.1152\/ajprenal.00306.2015","article-title":"The endothelial-to-mesenchymal transition and endothelial cilia in EPC-mediated postischemic kidney protection","volume":"310","author":"Patschan","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1681\/ASN.2006010017","article-title":"Update on mechanisms of ischemic acute kidney injury","volume":"17","author":"Devarajan","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40697-015-0062-9","article-title":"Acute kidney injury: Preclinical innovations, challenges, and opportunities for translation","volume":"2","author":"Silver","year":"2015","journal-title":"Can. J. Kidney Health Dis."},{"key":"ref_14","first-page":"25","article-title":"Renoprotective effect of erythropoietin via modulation of the STAT6\/MAPK\/NF-kappaB pathway in ischemia\/reperfusion injury after renal transplantation","volume":"41","author":"Zhang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5414\/CN106921","article-title":"Cytokines in acute kidney injury (AKI)","volume":"76","author":"Lee","year":"2011","journal-title":"Clin. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/jcp.22153","article-title":"Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: Involvement of ERK, JNK, AP-1, and NF-kappaB","volume":"224","author":"Yang","year":"2010","journal-title":"J. Cell Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1073\/pnas.91.2.812","article-title":"Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury","volume":"91","author":"Kelly","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"F897","DOI":"10.1152\/ajprenal.00643.2016","article-title":"Endothelial colony-forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury","volume":"312","author":"Collett","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00441-021-03473-0","article-title":"Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease","volume":"385","author":"Kurts","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_20","first-page":"3577","article-title":"The deficiency of CX3CL1\/CX3CR1 system ameliorates high fructose diet-induced kidney injury by regulating NF-kappaB pathways in CX3CR1-knock out mice","volume":"41","author":"Yu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.23876\/j.krcp.20.185","article-title":"T helper 17 cells in the pathophysiology of acute and chronic kidney disease","volume":"40","author":"Basile","year":"2021","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"F796","DOI":"10.1152\/ajprenal.00187.2020","article-title":"Mutation of RORgammaT reveals a role for Th17 cells in both injury and recovery from renal ischemia-reperfusion injury","volume":"319","author":"Mehrotra","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1124\/jpet.113.205732","article-title":"NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury","volume":"346","author":"Kim","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6277","DOI":"10.4049\/jimmunol.1002330","article-title":"An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury","volume":"185","author":"Shigeoka","year":"2010","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41419-018-0378-3","article-title":"Hydroxychloroquine attenuates renal ischemia\/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation","volume":"9","author":"Tang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2174\/1568008054863754","article-title":"Caspases as drug targets in ischemic organ injury","volume":"5","author":"Faubel","year":"2005","journal-title":"Curr. Drug Targets Immune Endocr. Metabol. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, X., Agborbesong, E., and Li, X. (2021). The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011253"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1159\/000101323","article-title":"The role of tubular epithelial-mesenchymal transition in progressive kidney disease","volume":"185","author":"Burns","year":"2007","journal-title":"Cells Tissues Organs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/nm.3901","article-title":"Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease","volume":"21","author":"Grande","year":"2015","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41419-020-03322-y","article-title":"Snai1-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2\/M arrest in the progression of renal fibrosis via NF-kappaB-mediated inflammation","volume":"12","author":"Qi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/sctm.19-0409","article-title":"Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open-label, controlled phase II clinical trial","volume":"9","author":"Yang","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1002\/sctm.20-0561","article-title":"Acute kidney injury successfully treated with autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation: A first-in-human report","volume":"10","author":"Suzuki","year":"2021","journal-title":"Stem Cells Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1546\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:22Z","timestamp":1760134222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031546"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031546","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}