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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MDPI AG
2023-09-01
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| author | Shao-Yu Tang Yi-Chin Lee Chien-Wei Tseng Po-Hsun Huang Ko-Lin Kuo Der-Cherng Tarng |
| author_facet | Shao-Yu Tang Yi-Chin Lee Chien-Wei Tseng Po-Hsun Huang Ko-Lin Kuo Der-Cherng Tarng |
| author_sort | Shao-Yu Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:58:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:22Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-170cd04aa2af4b3091c82c77fb352dde2023-11-19T17:43:42ZengMDPI AGPharmaceutics1999-49232023-09-011510238010.3390/pharmaceutics15102380Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney DiseaseShao-Yu Tang0Yi-Chin Lee1Chien-Wei Tseng2Po-Hsun Huang3Ko-Lin Kuo4Der-Cherng Tarng5Department of Medical Education, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, TaiwanDepartment of Physiology, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanDepartment of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, TaiwanInstitute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanSchool of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97004, TaiwanInstitute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanPatients 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.https://www.mdpi.com/1999-4923/15/10/2380chronic kidney diseasegranulocyte colony-stimulating factorendothelial progenitor cellneovascularization |
| spellingShingle | Shao-Yu Tang Yi-Chin Lee Chien-Wei Tseng Po-Hsun Huang Ko-Lin Kuo Der-Cherng Tarng Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease Pharmaceutics chronic kidney disease granulocyte colony-stimulating factor endothelial progenitor cell neovascularization |
| title | Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease |
| title_full | Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease |
| title_fullStr | Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease |
| title_full_unstemmed | Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease |
| title_short | Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease |
| title_sort | granulocyte colony stimulating factor improves endothelial progenitor cell mediated neovascularization in mice with chronic kidney disease |
| topic | chronic kidney disease granulocyte colony-stimulating factor endothelial progenitor cell neovascularization |
| url | https://www.mdpi.com/1999-4923/15/10/2380 |
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