Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms23031546
Keywords
acute kidney injury; chronic kidney disease; endothelial progenitor cell; epithelial-mesenchymal transition; inflammasome; ischemia-reperfusion injury; fibrosis
Funding
- National Research Foundation of Korea [NRF-2017R1D1A1B03036316, 2021R1F1A1061445]
- National Research Foundation of Korea [2021R1F1A1061445] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study demonstrates that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target for EPCs as a treatment for IRI-induced AKI and prevention of progression to CKD.
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-kappa B, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, ROR gamma t, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-beta, alpha-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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