Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have a higher prevalence of peripheral arterial disease (PAD), and endothelial progenitor cells (EPCs) play a pivotal role. We examined the impact of granulocyte colony-stimulating factor (G-CSF) on EPC function in response to tissue ischemia. Eight-week-ol...

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Published in:Pharmaceutics 2023-09, Vol.15 (10), p.2380
Main Authors: Tang, Shao-Yu, Lee, Yi-Chin, Tseng, Chien-Wei, Huang, Po-Hsun, Kuo, Ko-Lin, Tarng, Der-Cherng
Format: Article
Language:English
Subjects:
Antibodies
Aprotinin
chronic kidney disease
Chronic kidney failure
Comparative analysis
endothelial progenitor cell
Endothelium
Granulocyte colony-stimulating factor
Granulocytes
Hypoxia
Ischemia
Ketamine
Kidney diseases
Laboratory animals
Lasers
Mice
Neovascularization
Proteins
Stem cells
Sulfates
Surgery
Vascular endothelial growth factor
Veins & arteries
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Summary:Patients with chronic kidney disease (CKD) have a higher prevalence of peripheral arterial disease (PAD), and endothelial progenitor cells (EPCs) play a pivotal role. We examined the impact of granulocyte colony-stimulating factor (G-CSF) on EPC function in response to tissue ischemia. Eight-week-old male C57BL/6J male mice were divided into sham operation and subtotal nephrectomy (SNx) groups, received hindlimb ischemic operation after seven weeks, then randomly received G-CSF or PBS intervention for four weeks with weekly follow-ups. SNx mice had significantly reduced limb reperfusion, decreased plasma EPC mobilization, and impaired angiogenesis in ischemic hindlimbs compared to the control group. However, G-CSF increased IL-10 and reversed these adverse changes. Additionally, ischemia-associated protein expressions, including IL-10, phospho-STAT3, VEGF, and phospho-eNOS, were significantly downregulated in the ischemic hindlimbs of SNx mice versus control, but these trends were reversed by G-CSF. Furthermore, in cultured EPCs, G-CSF significantly attenuated the decrease in EPC function initiated by indoxyl sulfate through IL-10. Overall, we discovered that G-CSF can improve EPC angiogenic function through a hypoxia/IL-10 signaling cascade and impede neovascular growth in response to ischemia of SNx mice. Our results highlight G-CSF’s potential to restore angiogenesis in CKD patients with PAD via EPC-based methods.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15102380