섬유아세포에서 Smad2/3 발현 감소를 통한 Curcumin의 제1형 교원질 발현 억제

Abstract

Background: Imbalance among TGF-β/Smad pathway, MMP-1, and TIMP-1 expressions results in sclerotic skin disease, such as scleroderma, hypertrophic scar, and keloids. Curcumin, a phytochemical extracted from the rhizomes of Curcuma longa, showed an anti-fibrotic effect in an animal study, such as a pulmonary and cholangioductal fibrosis animal model. However, the expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 in curcumin treated human skin fibroblasts is largely unknown. Objective: The purpose of this study was to investigate the expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 proteins in curcumin-treated human skin fibroblasts. Methods: Human skin fibroblasts were treated by various concentrations of curcumin (1∼40 uM). The expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 proteins were analyzed by Western blot analysis. In addition, activities of type I collagen promoter were analyzed by the CAT assay. Results: The expression of type I collagen decreased but the expression of MMP-1 and TIMP-1 increased by curcumin treatment in a dose and time dependent manner in Western blot analysis. Type I collagen promoter activities were decreased by curcumin treatment in the CAT assay. Smad2/3 expression decreased by curcumin treatment but TGF-β1 induced Smad2/3 activation was not decreased by curcumin treatment following Western blot analysis. Conclusion: Decrease of type I collagen expression through the inhibition of Smad2/3 and increase of the expression of MMP-1, which is the degradating enzyme of type I collagen, in human skin fibroblasts by curcumin treatment offer expectation of curcumin as antifibrotic agent.