These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Effects of peroxisome proliferators-activated receptor gamma agonists on transforming growth factor-beta1 and Smads signal pathway: experiment with rat renal fibroblasts].
    Author: Wang WM, Liu F, Chen N.
    Journal: Zhonghua Yi Xue Za Zhi; 2006 Mar 21; 86(11):740-4. PubMed ID: 16681946.
    Abstract:
    OBJECTIVE: To study the effects of peroxisome proliferators-activated receptor gamma (PPARgamma) agonists on transforming growth factor (TGF)-beta1-induced fibrotic responses in renal fibroblasts, so as to investigate its effects in prevention of tubulointerstitial fibrosis. METHODS: Rat renal fibroblasts of the line NRK/49F were cultured and divided into groups. In group 1 TGFbeta1 of the concentrations of 0, 1, 2, 5, and 10 ng/ml was added and co-cultured for 24 h. In group 2 TGFbeta1 of the concentration of 5 ng/ml was added and co-cultured for 0, 6, 12, and 24 h respectively. Groups 3, 4, and 5 were pretreated with 10 micromol/L15d-PGJ2, PPARgamma ligand, 10 micromol/L troglitazone, agonist of, and 10 micromol/L ciglitazone, both PPARgamma agonists, respectively for 2 h, then treated with 5 ng/ml TGFbeta1. A blank control group was set up. The cultured cells were collected. RT-PCR was used to detect the mRNA expression of TGF-beta1-indued fibronectin (FN). Western blotting was used to detect the expression of TGF-beta1-induced FN, Smad, and phosphorylated Smad (p-Smad) proteins. RESULTS: TGF-beta1 enhanced the FN mRNA expression in a dose- and time-dependent manner. The FN mRNA expression of the 5 ng/ml TGF-beta1 group was 3.7 times that of the control group (P < 0.05). The FN mRNA expression of the 15d-PGJ2, troglitazone-, and ciglitazone-pretreated groups were lower than that of the 5 ng/ml TGF-beta1 group by 37.3%, 41.5%, and 22.7% respectively (all P < 0.05). The p-Smad2/3 protein expression levels of the TGF-beta1 group began to increase 15 minutes after stimulation, increased in a time-dependent manner, peaked 1 hour after, and began to decrease 2 hours later. However, the levels of protein expression of total Smad2 and Smad3 did not change significantly in all groups. Both 2 ng/ml TGFbeta1 and 5 ng/ml TGFbeta1 significantly induced the increase of protein expression of p-Smad2/3 (all P < 0.05). The levels of protein expression of p-Smad2 and p-Smad3 of the 5 ng/ml TGFbeta1 group were 3.42 and 0.97 times those of the 2 ng/ml TGFbeta1 (both P < 0.05). The levels of protein expression of p-Smad2/3 of the 15d-PGJ2, troglitazone-, and ciglitazone-pretreated groups were all significantly lower than that of the 5 ng/ml TGFbeta1 group by 61.2%, 53.0%, and 59.5% (all P < 0.05), However, there was no significant difference among different drug-treated groups (all P > 0.05). CONCLUSION: Possibly through abrogating TGF-beta1/Smads signaling pathway, PPARgamma agonists inhibit TGF-beta1-induced renal fibroblast extracellular matrix synthesis and may play a potential role in preventing tubulointerstitial fibrosis as a novel approach to prevent the progress of end stage renal dysfunction.
    [Abstract] [Full Text] [Related] [New Search]