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- Xiaowei Zheng
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Sampath Narayanan
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Vivekananda Gupta Sunkari
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Sofie Eliasson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Ileana Ruxandra Botusan
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Jacob Grünler
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Anca Irinel Catrina
- Department of Rheumatology, Karolinska University Hospital Solna, 17176 Stockholm, Sweden;
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- Freddy Radtke
- Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, 1015 Lausanne, Switzerland;
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- Cheng Xu
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Allan Zhao
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Neda Rajamand Ekberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
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- Urban Lendahl
- Department of Cell and Molecular Biology, Karolinska Institutet, 17165 Stockholm, Sweden;
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- Sergiu-Bogdan Catrina
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden;
抄録
<jats:title>Significance</jats:title> <jats:p>Diabetic foot ulcerations (DFUs) represent a major medical and economic problem with still-unclear pathogenic mechanisms. The Notch pathway plays a pivotal role in cell differentiation, proliferation, and angiogenesis, processes that are profoundly disturbed in diabetic wounds. Notch signalling is activated upon interactions between membrane-bound Notch receptors (Notch 1–4) and ligands (Jagged 1–2 and Delta-like 1, 3, 4). Here, we report that a specific positive Delta-like 4–Notch1 feedback loop is activated by high glucose levels and specifically impairs wound healing in diabetes. Local inhibition of Notch signalling in experimental wounds using chemical and genetic approaches markedly improves healing exclusively in diabetic, but not in nondiabetic, animals, making Notch1 signalling an attractive locally therapeutic target for the treatment of DFUs.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 116 (14), 6985-6994, 2019-03-18
Proceedings of the National Academy of Sciences