Suppression of TGF-β1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid.
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.
Hsu
Yi-Chiang
YC
Graduate Institute of Medical Science and Innovative Research Center of Medicine, College of Health Sciences, Chang Jung Christian University, No. 396. Sec. 1, Changrong Rd., Gueiren Township, Tainan 71101, Taiwan. d8702008@tmu.edu.tw
Chen
Ming-Jenn
MJ
Yu
Ya-Mei
YM
Ko
Shun-Yao
SY
Chang
Chi-Chang
CC
D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007627:Keloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D016326:Extracellular Matrix Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003474:Curcumin