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Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice

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 i...

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Autores principales: Jang, Ha Nee, Kim, Jin Hyun, Jung, Myeong Hee, Tak, Taekil, Jung, Jung Hwa, Lee, Seunghye, Jung, Sehyun, Chang, Se-Ho, Kim, Hyun-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835871/
https://www.ncbi.nlm.nih.gov/pubmed/35163466
http://dx.doi.org/10.3390/ijms23031546
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author Jang, Ha Nee
Kim, Jin Hyun
Jung, Myeong Hee
Tak, Taekil
Jung, Jung Hwa
Lee, Seunghye
Jung, Sehyun
Chang, Se-Ho
Kim, Hyun-Jung
author_facet Jang, Ha Nee
Kim, Jin Hyun
Jung, Myeong Hee
Tak, Taekil
Jung, Jung Hwa
Lee, Seunghye
Jung, Sehyun
Chang, Se-Ho
Kim, Hyun-Jung
author_sort Jang, Ha Nee
collection PubMed
description 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-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-β, α-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.
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spelling pubmed-88358712022-02-12 Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice Jang, Ha Nee Kim, Jin Hyun Jung, Myeong Hee Tak, Taekil Jung, Jung Hwa Lee, Seunghye Jung, Sehyun Chang, Se-Ho Kim, Hyun-Jung Int J Mol Sci Article 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-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-β, α-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. MDPI 2022-01-28 /pmc/articles/PMC8835871/ /pubmed/35163466 http://dx.doi.org/10.3390/ijms23031546 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jang, Ha Nee
Kim, Jin Hyun
Jung, Myeong Hee
Tak, Taekil
Jung, Jung Hwa
Lee, Seunghye
Jung, Sehyun
Chang, Se-Ho
Kim, Hyun-Jung
Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title_full Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title_fullStr Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title_full_unstemmed Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title_short Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
title_sort human endothelial progenitor cells protect the kidney against ischemia-reperfusion injury via the nlrp3 inflammasome in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835871/
https://www.ncbi.nlm.nih.gov/pubmed/35163466
http://dx.doi.org/10.3390/ijms23031546
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