Effects of tanshinone IIA on transforming growth factor beta1-Smads signal pathway in renal interstitial fibroblasts of rats.
The effects of tanshinone IIA (TSN) on transforming growth factor beta1 (TGFbeta1) signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of renal interstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured in vitro, stimulated with 5 ng/mL TGFbeta1 and pretreated with 10(-6), 10(-5), 10(-4) mol/L TSN respectively. The mRNA levels of fibronectin (FN) were examined by RT-PCR. The protein expression of FN and Smads was detected by Western blot. TGFbeta1 induced the expression of FN mRNA and Smads in a time-dependent manner in a certain range. Compared with pre-stimulation, the FN mRNA and protein levels were increased by 1.1 times and 1.5 times respectively (P<0.01, P<0.01), and the protein expression of phosphorylated Smad2/3 (p-Smad2/3) increased by 7 times at the end of TGFbeta1 stimulation (P<0.01). TSN pretreatment may down-regulate the FN and p-Smad2/3 expression in a dose-dependent manner. 10(-6) mol/L TSN pretreatment had no effect on the FN and p-Smad2/3 expression (both P>0.05). After pretreatment with 10(-5) and 10(-4) mol/L TSN, the FN mRNA levels were decreased by 28.1% and 43.8% respectively (P<0.05, P<0.01), the FN protein levels were decreased by 40% and 44% respectively (P<0.05, P<0.05), and the p-Smad2/3 protein expression were decreased by 40% and 65% respectively (P<0.05, P<0.01). The inhibitory effect of TSN on renal interstitial fibrosis may be related to its blocking effect on TGFbeta1-Smads signal pathway in renal interstitial fibroblasts.
Tang
Jinhui
J
Department of Pediatrics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. jinhuitang@tjh.tjmu.edu.cn
Zhan
Chengye
C
Zhou
Jianhua
J
D045784:Abietanes; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D007668:Kidney / Q000166:cytology / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
D045784:Abietanes; D005353:Fibronectins; D010616:Phenanthrenes; D012333:RNA, Messenger; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; C021751:tanshinone