AI Article Synopsis
- Keloids are tough, overgrown scars that are hard to treat, and the study explores how melatonin might help with them for the first time.
- Researchers used various lab techniques to study the effects of melatonin on keloid fibroblasts and found that it promotes cell death while inhibiting cell growth and other activities related to keloid formation.
- The results indicated that melatonin works through specific cellular pathways, and when combined with the drug 5-fluorouracil, it could enhance the inhibition of keloid fibroblasts even further, suggesting a potential new treatment strategy.
Article Abstract
Background: Keloids are abnormal fibrous hyperplasias that are difficult to treat. Melatonin can be used to inhibit the development of certain fibrotic diseases but has never been used to treat keloids. We aimed to discover the effects and mechanisms of melatonin in keloid fibroblasts (KFs).
Methods: Flow cytometry, CCK-8 assays, western blotting, wound-healing assays, transwell assays, collagen gel contraction assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of melatonin in fibroblasts derived from normal skin, hypertrophic scars and keloids. The therapeutic potential of the combination of melatonin and 5-fluorouracil (5-FU) was investigated in KFs.
Results: Melatonin significantly promoted cell apoptosis and inhibited cell proliferation, migration and invasion, contractile capability and collagen production in KFs. Further mechanistic studies demonstrated that melatonin could inhibit the cAMP/PKA/Erk and Smad pathways through the membrane receptor MT2 to alter the biological characteristics of KFs. Moreover, the combination of melatonin and 5-FU remarkably promoted cell apoptosis and inhibited cell migration and invasion, contractile capability and collagen production in KFs. Furthermore, 5-FU suppressed the phosphorylation of Akt, mTOR, Smad3 and Erk, and melatonin in combination with 5-FU markedly suppressed the activation of the Akt, Erk and Smad pathways.
Conclusions: Collectively, melatonin may inhibit the Erk and Smad pathways through the membrane receptor MT2 to alter the cell functions of KFs, while combination with 5-FU could exert even more inhibitory effects in KFs through simultaneous suppression of multiple signalling pathways.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977354 | PMC |
| http://dx.doi.org/10.1093/burnst/tkad005 | DOI Listing |
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