KY19382 Accelerates Cutaneous Wound Healing via Activation of the Wnt/β-Catenin Signaling Pathway. 2023

Minguen Yoon, and Eunhwan Kim, and Seol Hwa Seo, and Geon-Uk Kim, and Kang-Yell Choi
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

The Wnt/β-catenin signaling pathway plays important roles in the multi-phases of wound healing: homeostasis, inflammation, proliferative, and remodeling phases. However, there are no clinically available therapeutic agents targeting the Wnt/β-catenin pathway. In this study, we tested the effect of 5, 6-dichloroindirubin-3'-methoxime (KY19382), a small molecule that activates the Wnt/β-catenin pathway via interference with the function of the negative feedback regulator CXXC5, on cutaneous wound healing. KY19382 significantly enhanced cell migration of human keratinocytes and dermal fibroblasts with increased levels of β-catenin, phalloidin, Keratin 14, proliferating cell nuclear antigen (PCNA), Collagen I, and alpha-smooth muscle actin (α-SMA) by activating the Wnt/β-catenin signaling pathway without causing significant cytotoxicity. In addition, levels of Collagen I, Keratin 14, PCNA, and stem cell markers were significantly increased by KY19382 in a cutaneous murine wound healing model. Moreover, KY19382 treatment accelerated re-epithelialization and neo-epidermis formation with collagen deposition and stem cell activation at an early stage of cutaneous wound healing. Overall, KY19382 accelerates wound healing via activating the Wnt/β-catenin pathway, and may have the potential to be used for the development of a new wound healing agent.

UI MeSH Term Description Entries
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D051153 Wnt Proteins Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN. Wingless Type Protein,Wnt Factor,Wnt Protein,Wingless Type Proteins,Wnt Factors,Factor, Wnt,Protein, Wingless Type,Protein, Wnt,Type Protein, Wingless
D051176 beta Catenin A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS. beta-Catenin,Catenin, beta
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053547 Keratin-14 A type I keratin that is found associated with the KERATIN-5 in the internal stratified EPITHELIUM. Mutations in the gene for keratin-14 are associated with EPIDERMOLYSIS BULLOSA SIMPLEX. Cytokeratin 14,Cytokeratin-14,Keratin 14

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