ArticleThe Journal of investigative dermatology2021
High Glucose Restraint of Acetylcholine-Induced Keratinocyte Epithelial-Mesenchymal Transition Is Mitigated by p38 Inhibition.
Article in The Journal of investigative dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Negative-Pressure Induces Epithelial-Mesenchymal Transition via Thrombospondin-1 Upregulation in Intact Diabetic Skin.International wound journal · 2026Article
- Review
- YWHAG Deficiency Disrupts the EMT-Associated Network to Induce Oxidative Cell Death and Prevent Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Epithelial-Mesenchymal Plasticity and Endothelial-Mesenchymal Transition in Cutaneous Wound Healing.Cold Spring Harbor perspectives in biology · 2023Review
- The Epidermal Keratinocyte as a Therapeutic Target for Management of Diabetic Wounds.International journal of molecular sciences · 2023Review
- Driving adult tissue repair via re-engagement of a pathway required for fetal healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions.Molecular medicine (Cambridge, Mass.) · 2022Article
- The Hyperglycemia Stranglehold Stifles Cutaneous Epithelial‒Mesenchymal Plasticity and Functional Wound Closure.The Journal of investigative dermatology · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-neuronal acetylcholine (Ach) plays important roles in various aspects of cell biology and homeostasis outside the neural system. Keratinocytes (KCs) have a functional cholinergic mechanism, suggesting that they respond to Ach. However, the physiological role and mechanism by which Ach modulates wound KC behavior in both nondiabetic and diabetic conditions are unexplored. We found an enrichment in neurotransmitter-related pathways in microdissected-migrating nondiabetic and diabetic KCs. We showed that Ach upregulated TGFβRII through Src-extracellular signal‒regulated kinase 1/2 pathway to potentiate TGFβ1-mediated epithelial‒mesenchymal transition in normoglycemic condition. Unexpectedly, KCs were nonresponsive to the elevated endogenous Ach in a hyperglycemic environment. We further showed that the activation of p38 MAPK in high glucose condition interferes with Src-extracellular signal‒regulated kinase 1/2 signaling, resulting in Ach resistance that could be rescued by inhibiting p38 MAPK. A better understanding of the cholinergic physiology in diabetic KCs could improve wound management and care. The finding suggests that mitigating the inhibitory effect of diabetic wound microenvironment has a direct clinical implication on the efficacy and safety of various wound healing agents to improve chronic diabetic wounds.
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Registered trials
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