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Publication : Protein tyrosine phosphatase 1B impairs diabetic wound healing through vascular endothelial growth factor receptor 2 dephosphorylation.

First Author  Zhang J Year  2015
Journal  Arterioscler Thromb Vasc Biol Volume  35
Issue  1 Pages  163-74
PubMed ID  25395617 Mgi Jnum  J:236588
Mgi Id  MGI:5806407 Doi  10.1161/ATVBAHA.114.304705
Citation  Zhang J, et al. (2015) Protein tyrosine phosphatase 1B impairs diabetic wound healing through vascular endothelial growth factor receptor 2 dephosphorylation. Arterioscler Thromb Vasc Biol 35(1):163-74
abstractText  OBJECTIVE: Impaired wound healing is a major complication of diabetes mellitus. The mechanisms that govern wound healing, however, are complex and incompletely understood. In the present study, we determined the inhibitory role of protein tyrosine phosphatase 1B (PTP1B) in the process of diabetic wound healing. APPROACH AND RESULTS: First, by comparing the wound healing process in PTP1B knockout (PTP1B(-/-)) mice, ob/ob mice and their wild-type littermates in the presence or absence of streptozotocin treatment, we showed that the inhibition of mouse wound healing in streptozotocin-induced diabetic conditions is because of the upregulation and activation of PTP1B. Second, the impaired wound healing in ob/ob mice and streptozotocin-treated wild-type mice was rescued by a PTP1B inhibitor. Third, PTP1B, which is upregulated under hyperglycemic condition, inhibited the tube formation, proliferation, and migration of human microvascular endothelial cells induced by vascular endothelial growth factor, whereas this inhibition was largely abolished by the PTP1B inhibitor. Finally, mechanism study further indicated that PTP1B likely suppressed the proliferation, migration, and tube formation of vascular endothelial cells through dephosphorylation of vascular endothelial growth factor receptor 2. CONCLUSIONS: Our study demonstrated that PTP1B negatively modulated the diabetic wound healing process by dephosphorylating the endothelial cell vascular endothelial growth factor receptor 2 and that the specific inhibitor of PTP1B might serve as a potential novel therapeutic tool for diabetic wound healing.
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