Vascular Endothelial Growth Factor Receptor Type 1 Signaling Prevents Delayed Wound Healing in Diabetes by Attenuating the Production of IL-1β by Recruited Macrophages.

Vascular Endothelial Growth Factor Receptor Type 1 Signaling Prevents Delayed Wound Healing in Diabetes by Attenuating the Production of IL-1β by Recruited Macrophages. Am J Pathol. 2016 Apr 13; Authors: Okizaki SI, Ito Y, Hosono K, Oba K, Ohkubo H, Kojo K, Nishizawa N, Shibuya M, Shichiri M, Majima M Abstract The persistence of proinflammatory macrophages, which are recruited to the granulation tissue, impairs the healing of diabetic wounds. Herein, we examined the role of vascular endothelial growth factor receptor type 1 (VEGFR1) signaling in streptozotocin (STZ)-induced diabetic wound healing. Angiogenesis, lymphangiogenesis, and the healing of full-thickness skin wounds were impaired in STZ-treated wild-type (WT) mice compared with vehicle-treated WT mice, with attenuated recruitment of VEGFR1-positive macrophages expressing vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D to the wound granulation tissue. These phenomena were even more prevalent in STZ-treated VEGFR1 tyrosine kinase knockout mice (VEGFR1 TK(-/-) mice). STZ-treated WT mice, but not STZ-treated VEGFR1 TK(-/-) mice, showed accelerated wound healing when treated with placenta growth factor. Compared with that of STZ-treated WT mice, the wound granulation tissue of STZ-treated VEGFR1 TK(-/-) mice contained more VEGFR1-positive cells expressing IL-1β [a classic (M1) activated macrophage marker] and fewer VEGFR1-positive cells expressing the mannose...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research