Healing the diabetic wound: Unlocking the secrets of genes and pathways

Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-β, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/β-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.