curcumin and Keloid

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs.

Topics: Cell Proliferation; Curcumin; Extracellular Matrix; Fibroblasts; Humans; Interleukin-6; Keloid; Reactive Oxygen Species; STAT3 Transcription Factor

Topics: Curcumin; Dermatitis, Contact; Extracellular Matrix; Fibroblasts; Humans; Keloid; Quercetin

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis. It is a late spreading skin overgrowth and may be considered a plastic surgeon's nightmare. In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC). Curcuminoids have been found to inhibit fibrosis. However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear. In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-β1. A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells. The level of ECM in the primary KFs was elevated. The elevation of ECM and TGF-β1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs. The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.

Topics: Adult; Aged; Cell Culture Techniques; Cells, Cultured; Chromatography, High Pressure Liquid; Curcumin; Extracellular Matrix Proteins; Female; Fibroblasts; Humans; Keloid; Male; Middle Aged; Signal Transduction; Smad Proteins; Transforming Growth Factor beta; Up-Regulation

Keloid and hypertrophic scars commonly occur after injuries. Overproliferation of fibroblasts, overproduction of collagen, and contraction characterize these pathologic scars. Current treatment of excessive scars with intralesional corticosteroid injections used individually or in combination with other methods often have unsatisfactory outcome, frustrating both the patient and the clinician. The phytochemical compounds are well known as potential anticancer agents. We have investigated the inhibitory effects of compounds on keloid fibroblasts (KF) and hypertrophic scar-derived fibroblasts (HSF).. Fibroblasts were cultured from nontreated earlobe keloids and burn hypertrophic scars. Ten compounds (three hydroxybenzoic and four hydroxycinnamic acid derivatives, two flavonols [quercetin and kaempferol], and turmeric curcumin) were tested with fibroblasts. The inhibitory effects of compounds on fibroblasts was assessed by proliferation assays, fibroblast-populated collagen lattice (FPCL) contraction, and electron microscopy.. The phytochemicals significantly inhibited KF and HSF proliferation in a dose- and time-dependent manner. In the hydroxybenzoic and flavonol groups, increasing inhibitory effects seemed to depend on increasing numbers of hydroxyl groups in their chemical structures. This phenomenon was not observed in the hydroxycinnamic acid group. The phytochemicals inhibited fibroblast proliferation by inducing cell growth arrest but not apoptosis. The reversibility of growth inhibition occurred when the compounds were removed from the culture and fresh media was replaced. Slower reversibility of growth inhibition was observed in the groups treated with quercetin, chlorogenic acid, or curcumin. The compounds quercetin, gallic acid, protocatechuic acid, and chlorogenic acid were the strongest inhibitors of FPLC contraction by HTFs. When the compounds were washed out of the lattices and replaced by fresh medium, the FPCL contraction was resumed. The resumption of FPCL contraction was slowest in the quercetin-treated group, indicating again the strong inhibitory effect of quercetin.. From this in vitro study, quercetin seemed to have good potent effects to inhibit proliferation and contraction of excessive scar-derived fibroblasts.

Topics: Adolescent; Biological Assay; Burns; Cell Division; Cells, Cultured; Cicatrix, Hypertrophic; Collagen; Coumaric Acids; Curcumin; Ear; Enzyme Inhibitors; Female; Fibroblasts; Flavonoids; Flavonols; Humans; Hydroxybenzoates; Kaempferols; Keloid; Quercetin