Wnt7a promotes wound healing by regulation of angiogenesis and inflammation: Issues on diabetes and obesity

Background: Diabetic skin heals wounds poorly. Though obesity is the common risk factor of diabetes mellitus, few studies have investigated its effects on wound healing. Objectives: This study aimed to evaluate the morphology and possible mechanism of human umbilical vein endothelial cells (HUVEC-C) in response to different levels of glucose and palmitic acid, and explore the role of Wnt7a in wound healing. Methods: The functional changes of HUVEC-C and mRNA expression of Wnt signaling were determined by analyzing cell viability, migration, tube formation and rt-PCR in gradients of glucose and palmitic acid. Recombinant Wnt7a protein was injected around wounds made on streptozotocin (STZ) -induced diabetic rats with (HF) or without (DM) high-fat diet. Angiogenesis and inflammatory statement were mainly analyzed by immunohistochemistry, ELISA, cytometry and Western blotting. Results: The expression of Wnt7a significantly decreased in high Glc/PA cultured cells or DM and HF wounded rats. Impaired wound healing was also observed in DM and HF groups. The healing rate significantly accelerated after localized injection with Wnt7a at d10. Moreover, the expression of CD31, eNOS phosphorylation and NO were increased; the reduction of local neutrophils influx, ICAM-1 and IL6/8 expression levels were obvious especially in diabetic with obesity rats at d10 after Wnt7a treatment. Conclusion: This study indicates the potential role of Wnt7a, which is beneficial for regeneration of damaged vessels, moderation of inflammatory statement in diabetic wound healing with or without obesity, thus demonstrating its possible utility as a topical administration to promote healing rate. (C) 2018 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.