Carvacrol Inhibits the Proliferation and Extracellular Matrix Deposition of Keloid Fibroblasts Through Nrf2/GPX4 and TGF-β1/Smad Signaling Pathways

Chunxia Zhang, Aili Cui, Xinghua Yuan and Zhehu Jin

Background and Objective: Keloid (KD) is a kind of fiber proliferative disease, usually caused by abnormal wound healing after a burn, trauma or infection and characterized by proliferation of cells and excessive deposition of extracellular matrix (ECM) in keloid fibroblasts (KFs). This study investigated the effect of carvacrol (CV) on the proliferation and ECM deposition of KFs. Materials and Methods: The proliferation of KFs was determined by scratch assay and cloning assay. The contents of iron, MDA and GSH were measured in KFs. The expressions of Nrf2/GPX4 and TGF-β1/Smad proteins were detected using Western blotting. All data were analyzed by GraphPad Prism 9.0 software. Results: The CV showed the ability to inhibit cell proliferation and migration, it promoted the expressions of iron and MDA and inhibited the expression of GSH in KFs. The CV promoted ferroptosis of KFs by inhibiting the protein expressions of Nrf2, HO-1, GPX4 and xCT. It also inhibited collagen deposition of KFs by inhibiting protein levels of collagen I, collagen III, fibronectin, α-SMA, p-Smad2 and p-Smad3. Conclusion: The CV promoted ferroptosis of KFs by regulating Nrf2/GPX4 signaling pathway to inhibit cell proliferation and regulated TGF-β1/Smad signaling pathway to inhibit ECM deposition.

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