title: Safflower extract: a novel renal fibrosis antagonist that functions by suppressing autocrine TGF-beta.
abstract: Progressive renal disease is characterized by the accumulation of extracellular matrix proteins in the renal interstitium. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers. The present study investigated the blood-circulation-promoting Chinese herb, safflower, on fibrosis status in NRK-49F cells, a normal rat kidney interstitial fibroblast, to evaluate the underlying signal transduction mechanism of transforming growth factor-beta (TGF-beta), a potent fibrogenic growth factor. Safflower was characterized and extracted using water. Renal fibrosis model was established both in vitro with fibroblast cells treated with beta-hydroxybutyrate and in vivo using rats undergone unilateral ureteral obstruction (UUO). Western blotting was used to examine protein expression in TGF-beta-related signal proteins such as type I and type II TGF-beta receptor, Smads2/3, pSmad2/3, Smads4, and Smads7. ELISA was used to analyze bioactive TGF-beta1 and fibronectin levels in the culture media. Safflower extract (SE) significantly inhibited beta-HB-induced fibrosis in NRK cells concomitantly with dose-dependent inhibition of the type I TGF-beta1 receptor and its down-stream signals (i.e., Smad). Moreover, SE dose-dependently enhanced inhibitory Smad7. Thus, SE can suppress renal cellular fibrosis by inhibiting the TGF-beta autocrine loop. Moreover, remarkably lower levels of tissue collagen were noted in the nephron and serum TGF-beta1 of UUO rats receiving oral SE (0.15 g/3 ml/0.25 kg/day) compared with the untreated controls. Hence, SE is a potential inhibitor of renal fibrosis. We suggest that safflower is a novel renal fibrosis antagonist that functions by down-regulating TGF-beta signals.
authors.affiliation: Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan. call0955443221@gmail.com
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Yang
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Chang
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Teng
authors.forename: Yi-Shiuan
authors.initials: YS
authors.lastname: Liu
authors.forename: Tao-Chen
authors.initials: TC
authors.lastname: Lee
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Tung-Nan
authors.initials: TN
authors.lastname: Liao
authors.forename: Jau-Shyang
authors.initials: JS
authors.lastname: Huang
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yeh
authors.forename: Wen-Teng
authors.initials: WT
authors.lastname: Chang
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Hung
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Wang
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chiang
authors.forename: Chien-Ya
authors.initials: CY
authors.lastname: Hung
authors.forename: Tsung-Jen
authors.initials: TJ
authors.lastname: Hung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism*; D005355:Fibrosis / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008516:Medicine, Chinese Traditional; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D005353:Fibronectins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1