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

International Journal of Molecular Sciences

Myeong Hee Jung¹  Seunghye Lee²  Sehyun Jung²  Hyun-Jung Kim²  Ha Nee Jang²  Se-Ho Chang²  Taekil Tak³  Jin Hyun Kim⁴  Jung Hwa Jung⁴ 

[1] Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Korea;Division of Nephrology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Korea;Gyeongnam Biohealth Research Center, Korea Institute of Toxicology, Jinju 52834, Korea;Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea;

关键词: acute kidney injury;    chronic kidney disease;    endothelial progenitor cell;    epithelial-mesenchymal transition;    inflammasome;    ischemia-reperfusion injury;   

DOI  :  10.3390/ijms23031546

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown