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Iranian Journal of Basic Medical Sciences، جلد ۲۸، شماره ۱۱، صفحات ۱۵۸۹-۱۵۹۷
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عنوان انگلیسی Elucidating the effect of deferoxamine, a hypoxia mimetic agent, on angiogenesis restoration in endothelial progenitor cells (EPCs) from diabetic mice
چکیده انگلیسی مقاله Objective(s): Diabetes increases the risk of heart disease and stroke, primarily through endothelial cell dysfunction and vascular damage. These vascular complications are partly due to defects in endothelial progenitor cells (EPCs). This study explores the efficacy of pharmacological priming of bone marrow EPCs (BMEPCs) with Deferoxamine (DFO), a hypoxia mimetic agent, in restoring dysregulated angiogenic pathways in streptozotocin (STZ)-induced mice with type-1 diabetes (T1D).Materials and Methods: BMEPCs were isolated from both normal and STZ-induced mice with T1D. The effects of an optimal concentration of DFO (80 µM) on the viability, proliferation, and tubulogenesis of EPCs were assessed. Furthermore, the probable beneficial effects of the conditioned medium from EPCs treated in the presence and absence of DFO were examined in mice (T1D) wound healing models.Results: DFO (80 µM) increased cell viability, proliferation, and tubulogenesis. EPCs isolated from diabetic mice showed significant impairments in the expression of HIF-1α, VEGF, and SDF-1 proteins compared to controls. DFO-preconditioning significantly enhanced protein expression of these genes. The conditioned medium from diabetic EPCs treated with DFO had a substantially greater favorable effect on wound healing in diabetic mice, connected with elevated levels of HIF-1α, VEGF, phosphorylated Tie2/Tie2, and Ang1.Conclusion: DFO reactivates proliferation and restores the impaired angiogenic properties of EPCs from diabetic mice by stabilizing HIF-1α and VEGF. Additionally, DFO enhanced the pro-angiogenic activity in the EPC-secretome, leading to improved wound healing. This improvement is attributed to the dual activation of HIF-1α /VEGF and Ang-1/Tie2 pathways, which are crucial for initiating and maturing new blood vessels.
کلیدواژه‌های انگلیسی مقاله Deferoxamine, Diabetes, Endothelial progenitor cell HIF-α, Tie2, VEGF
نویسندگان مقاله | Vahid Siavashi
Department of Pharmacology and Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran|Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran


| Seyed Mahdi Nassiri
Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran


| Mahdi Farhadi Mahalli
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran


| Tunku Kamarul
Tissue Engineering Group (NOCERAL), Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia


| Ali Sharifi
Department of Pharmacology and Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran|Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran|Stem cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran|Tissue Engineering Group (NOCERAL), Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
نشانی اینترنتی https://ijbms.mums.ac.ir/article_26664.html
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