ArticleMolecular medicine (Cambridge, Mass.)2023
The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- Endothelial ferroptosis: a novel mechanism and therapeutic target in diabetic microvascular complications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Mechanisms of Okanin against wound healing based on network pharmacology, molecular docking and molecular dynamics simulation.Scientific reports · 2025Article
- Ferroptosis in diabetes mellitus and its complications: overview of clinical and preclinical research.Cell death discovery · 2025Review
- miR-191-5p inhibits angiogenesis in diabetic foot ulcers wound healing via regulating VEGFA.European journal of medical research · 2025Article
- Thermoresponsive antioxidant metal-free carbon nanodot hydrogel: An effective therapeutic approach for ocular surface disease.Science advances · 2025Article
- RNA NCell death & disease · 2025Article
- Single-cell multi-omics dissection of c-Myb/AURKA-mediated autophagy and metabolic reprogramming in diabetic adipose-derived stem cells.Frontiers in immunology · 2025Article
- Enhancing radiotherapy in triple-negative breast cancer with hesperetin-induced ferroptosis via AURKA targeting nanocomposites.Journal of nanobiotechnology · 2024Article
- Genipin inhibits proliferation of gastric cancer cells by inducing ferroptosis: an integrated study of network pharmacology and bioinformatics study.Medical oncology (Northwood, London, England) · 2024Article
- Mesenchymal stem cell-derived extracellular vesicles accelerate diabetic wound healing by inhibiting NET-induced ferroptosis of endothelial cells.International journal of biological sciences · 2024Article
- Autophagy, Pyroptosis and Ferroptosis are Rising Stars in the Pathogenesis of Diabetic Nephropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
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7 authors at 1 institution in 1 country.
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Abstract
backgroundDiabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear.
methodHuman microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L D-glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo.
resultsIn our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation.
conclusionsThese results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.
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