Keloids are characterised by the excessive accumulation of extracellular matrix (ECM), especially overabundant collagen formation. In keloid fibroblasts (KFs), transforming growth factor (TGF)-β-dependent signalling is closely associated with a variety of keloid pathologic responses such as ECM production and fibroblast overgrowth. Thus, inhibition of TGF-β signalling would be a potential therapeutic approach to prevent keloid scar formation. Thereby, we aimed to identify a novel TGF-β signalling blocker among natural products using a simplified screening approach. We discovered that the extract of Aneilema keisak (A.K-Ex) lowered TGF-β-dependent signalling by reducing Smad2 protein levels. Given that KFs showed altered dependency on TGF-β for survival and proliferation, A.K-Ex-mediated reduction in Smad2 protein levels significantly inhibited the major characteristics of KFs such as cell growth, migration and collagen synthesis, suggesting that A.K-Ex exhibits possible therapeutic activity on keloids.
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http://dx.doi.org/10.1111/exd.12063 | DOI Listing |
Int J Mol Sci
January 2024
Department of Molecular Medicine, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.
Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease.
View Article and Find Full Text PDFPharm Biol
March 2015
Department of Pharmaceutical and Industrial, Pharmaceutical Technology , Chulalongkorn University, Bangkok , Thailand .
Context: Keloid is an excessive dermal scar occurring in response to skin injuries. Several therapeutic strategies have been proposed to ease the aggressiveness of keloid scarring. Even though the principle mechanism underlying the disease propagation still remains unidentified, several signaling pathways were highly focused as plausible pathways involving keloid formation, including transforming growth factor-beta 1 (TGF-β1), mitogen-activated protein kinase (MAPK), insulin-like growth factor-I (IGF-I), and integrin pathways.
View Article and Find Full Text PDFKeloids are characterised by the excessive accumulation of extracellular matrix (ECM), especially overabundant collagen formation. In keloid fibroblasts (KFs), transforming growth factor (TGF)-β-dependent signalling is closely associated with a variety of keloid pathologic responses such as ECM production and fibroblast overgrowth. Thus, inhibition of TGF-β signalling would be a potential therapeutic approach to prevent keloid scar formation.
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