ArticleThe Journal of investigative dermatology2014
Acute wounding alters the beta2-adrenergic signaling and catecholamine synthetic pathways in keratinocytes.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Sympathetic nerve aggravates autoimmune skin disease via NE-adrenergic receptor axis: Neuroimmune cross-talk insights from vitiligo.Science advances · 2026Article
- Targeting β2-adrenergic receptor reduces UV-induced cutaneous damage and inflammation in a murine model.Journal of photochemistry and photobiology · 2025Article
- Effects of topical isoxsuprine ointment on imiquimod-induced psoriasiform skin inflammation in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Recent advances in the role of neuroregulation in skin wound healing.Burns & trauma · 2025Review
- Article
- GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular Respiration.The Journal of investigative dermatology · 2024Article
- Topical Anti-ulcerogenic Effect of the Beta-adrenergic Blockers on Diabetic Foot Ulcers: Recent Advances and Future Prospectives.Current diabetes reviews · 2024Review
- An Overview of the Biological Complexity of Vitiligo.Oxidative medicine and cellular longevity · 2024Review
- Sympathetic System in Wound Healing: Multistage Control in Normal and Diabetic Skin.International journal of molecular sciences · 2023Review
- Article
- Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.American journal of clinical dermatology · 2021Review
- [Mechanisms of adrenergic β-antagonist for wounds and its application prospect in diabetic foot ulcers].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2020Review
- Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture.International journal of molecular sciences · 2020Article
- Combination product of dermal matrix, human mesenchymal stem cells, and timolol promotes diabetic wound healing in mice.Stem cells translational medicine · 2020Article
- Prolactin may serve as a regulator to promote vocal fold wound healing.Bioscience reports · 2020Article
- Article
- Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds.Advances in wound care · 2019Article
- The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined Burn and Radiation Wounds.Radiation research · 2018Article
- Systems biology of facial development: contributions of ectoderm and mesenchyme.Developmental biology · 2017Article
- Efficacy of Topical Timolol versus Saline in Chronic Venous Ulcers: A Randomized Controlled Trial.Journal of cutaneous and aesthetic surgeryArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Keratinocyte migration is critical for wound re-epithelialization. Previous studies showed that epinephrine activates the beta2-adrenergic receptor (B2AR), impairing keratinocyte migration. Here, we investigated the keratinocyte catecholamine synthetic pathway in response to acute trauma. Cultured keratinocytes were scratch wounded and expression levels of the B2AR and catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were assayed. The binding affinity of the B2AR was measured. Wounding downregulated B2AR, tyrosine hydroxylase, and phenylethanolamine-N-methyltransferase expression, but pre-exposure to timolol, a beta-adrenergic receptor antagonist, delayed this effect. In wounded keratinocytes, B2AR-binding affinity remained depressed even after its expression returned to prewounding levels. Keratinocyte-derived norepinephrine increased after wounding. Norepinephrine impaired keratinocyte migration; this effect was abrogated with B2AR-selective antagonist ICI-118,551 but not with B1AR-selective antagonist bisoprolol. Finally, for clinical relevance, we determined that norepinephrine was present in freshly wounded skin, thus providing a potential mechanism for impaired healing by local B2AR activation in wound-edge keratinocytes. Taken together, the data show that keratinocytes modulate catecholamine synthetic enzymes and release norepinephrine after scratch wounding. Norepinephrine appears to be a stress-related mediator that impairs keratinocyte migration through activation of the B2AR. Future therapeutic strategies evaluating modulation of norepinephrine-related effects in the wound are warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.