Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels

Abstract

Ischemic wound healing remains an unsolved problem with no previously identified molecular target for therapeutic intervention. This study demonstrates that VEGF-C overexpression by fibroblasts stimulates multiple biologic processes known to impact wound healing, such as collagen constriction, capillary sprouting, and EPC invasion and migration through extracellular matrix. Most ischemic wounds fail to heal and frequently lead to major limb amputation. Available cytokine ointments are ineffective, and revascularization is often not technically feasible. Even when these procedures are accomplished, many ischemic wounds frequently still do not heal because of multifactorial tissue level impairments in the fibroblastic and neovascularization responses at the wound base. Our findings identify an important role for two novel tissue level targets, dermis-derived fibroblasts and VEGF-C, in collagen constriction, angiogenesis, and postnatal vasculogenesis from BMD EPCs. Thus the findings are particularly relevant to the unsolved clinical problem of ischemic wound healing.

Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats

“…This agrees with previous studies stating that fibroblasts that express large amounts of VEGF may trigger collagen formation. (24) One limitation of the present study is that we did not determine the concentrations of PDGF and transforming growth factor (TGF) that are potent mediators of fibroblast activation in collagen synthesis. We also did not measure VEGF concentrations at baseline and at the end of the interventions to determine their relationship with the inflammatory and remodeling phases.…”

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

“…Angiogenesis is the process by which resident EC of the wound's adjacent mature vascular network, in response to angiogenic signals, proliferate, migrate, and remodel into new capillaries that grow within the wound substrate [35][36][37][38][39].…”

A fusion protein with the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment: Simultaneous blocking of VEGF receptor-1 and 2

“…Feng-Jen Tseng, 1, † Yu-Cheng Chen, 2, † Yu-Ling Lin, 2 Nu-Man Tsai, 3, † Ru-ping Lee, 4 Yo-shong Chung, 5 Chia-hung Chen, 2 Yen-Ku Liu, 2 Yu-shan huang, 5 Chia-hsiang hwang, 6,7 Yiu-Kay Lai 6 and Kuang-Wen Liao 5, adhesion and migration. 5 Both VEGF-C and VEGF-D bind to VEGFR-2 and VEGFR-3 and regulate lymph-angiogenesis and VEGF-C may also be involved in wound healing.…”

“…5 Both VEGF-C and VEGF-D bind to VEGFR-2 and VEGFR-3 and regulate lymph-angiogenesis and VEGF-C may also be involved in wound healing. 6,7 In addition, alternative exon splicing of human VEGF-A gene shows that it is comprised eight exons, denoted as: VEGF-A121, VEGF-A145, VEGF-A165, VEGF-A165b, VEGF-A189 and VEGF-A206. 8 VEGFs initiate signals through two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, 9 which are involved in the regulation of extracellular matrix degradation, cell adhesion and migration.…”