Safflower extract: a novel renal fibrosis antagonist that functions by suppressing autocrine TGF-beta.
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.
Yang
Yu-Lin
YL
Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan. call0955443221@gmail.com
Chang
Shan-Yu
SY
Teng
Hsiang-Chun
HC
Liu
Yi-Shiuan
YS
Lee
Tao-Chen
TC
Chuang
Lea-Yea
LY
Guh
Jinn-Yuh
JY
Chang
Fang-Rong
FR
Liao
Tung-Nan
TN
Huang
Jau-Shyang
JS
Yeh
Jeng-Hsien
JH
Chang
Wen-Teng
WT
Hung
Min-Yuan
MY
Wang
Ching-Jen
CJ
Chiang
Tai-An
TA
Hung
Chien-Ya
CY
Hung
Tsung-Jen
TJ
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
D005353:Fibronectins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1