Wnt Signaling Modulation in Chronic Wounds

Hannah Barge, Tennessee State University


The Wingless related integrated site 1 (Wnt) signaling pathway is quiescent in many mammalian organs and gets activated in response to injury. Wnt signaling promotes fibrotic wound healing following acute cutaneous injury by epithelial migration, differentiation and myofibroblast activation. Topical application of Wnt signaling inhibitor molecules promote regenerative cutaneous repair following acute injury. However, there is minimal detailed knowledge in our understanding of Wnt signaling activation in chronic non-healing human wounds. This thesis is focused on delineating the impact of canonical Wnt signaling modulation in chronic wounds using animal models of wound healing, samples from human patients, and cell line models in combination with Wnt signaling inhibitors. Full thickness excisional and incisional wounds in Streptozotocin (STZ)-induced type I diabetic mice activated Wnt signaling in both dermal and epidermal layers identified by ꞵ-catenin immunohistological staining and axis inhibition protein 2 (AXIN2) transcript levels. We have selected a panel of human chronic wound pathologies which include diabetic ulcer, burns, keloids, hypertrophic scars, and melanoma re-excision wounds to screen for fibrosis, endothelial markers, collagen deposition and ꞵ-catenin (Wnt signaling) activation. We have found that in treating fibroblast cell lines, our experimental Wnt signaling inhibitor ICG-001 completely blocks ꞵ-catenin production while XAV-939, also a Wnt signaling inhibitor, only partially decreases this protein. The goal of this research is to demonstrate that canonical Wnt signaling pathway inhibition could promote regenerative repair with minimal scarring in chronic human wounds. Our hope is that this work will contribute to the creation of personalized therapy to treat chronic wounds.

Subject Area

Biology|Cellular biology|Molecular biology

Recommended Citation

Hannah Barge, "Wnt Signaling Modulation in Chronic Wounds" (2023). ETD Collection for Tennessee State University. Paper AAI30570302.