Abstract
Background: This study tested the hypothesis that peripheral blood-derived endothelial progenitor cell (PBDEPC) therapy can impede the deterioration of chronic kidney disease (CKD) induced by 5/6 nephrectomy in rats. Methods and results: Adult-male rats (n = 30) were equally categorized into group 1 (sham control), group 2 (CKD only) and group 3 [CKD + PBDEPC (left intra-arterial (3.3 × 105) and penile vein (6.7 × 105) injections by day 14 after CKD induction]. By day 60, kidney blood fow (KBF) was significantly lower in group 2 than that in groups 1 and 3, and significantly lower in group 3 than that in group 1, whereas the levels of serum creatinine, and kidney injury score and size showed an opposite pattern compared to that of KBF among all groups (all p < 0.001). Protein expressions of apoptotic (caspase 3, PARP), infammatory (TNF-α, MMP-9), oxidative-stress (oxidized protein, NOX-1), fbrotic (Smad3, TGF-β), and hypoxic/ischemic cell-stress (HIF-1α, p-Akt) biomarkers showed an opposite pattern, whereas angiogenesis at protein (eNOS, CD31) and cellular (CD31+, CXCR4+) levels showed an identical pattern compared to that of blood fow in all groups (all p < 0.01). Other pro-angiogenic biomarkers (SDF-1α, CXCR4, VEGF) at protein and cellular levels and antioxidants (HO-1+, NQO 1, GR+) at cellular level showed progressive significant increase from groups 1 to 3 (all p < 0.001). Conclusion: The results support that PBDEPC therapy effectively inhibits the propagation of CKD and the deterioration of renal function through enhancement of angiogenesis, blood fow, and anti-oxidative capacity as well as suppression of infammation, oxidative stress, apoptosis, and fbrosis in a rodent model.
| Original language | English |
|---|---|
| Pages (from-to) | 804-824 |
| Number of pages | 21 |
| Journal | American Journal of Translational Research |
| Volume | 7 |
| Issue number | 5 |
| State | Published - 07 07 2015 |
Bibliographical note
Publisher Copyright:© 2015, E-Century Publishing Corporation. All Rights Reserved.
Keywords
- 5/6 nephrectomy
- Angiogenesis
- Apoptosis
- Chronic kidney disease
- Infammation
- Oxidative stress