Down-regulation of the expression of angiotensin II type 1 receptor in neonatal rat cardiac fibroblast by activation of PPARgamma signal pathway.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is one of the hormone nuclear receptors. Recent data have shown that activation of PPARgamma signal pathway has many positive effects on cardiovascular system. The goals of this study were to determine whether PPARgamma activator affects cardiac fibrosis and the possible mechanisms. Cardiac fibroblasts (CFs) of SD neonate rats were used in the study. Cells were divided into 4 groups: I--control group; II--pioglitazone group (Piog--PPARgamma agonist); III--angiotensin II (Ang II) group; and IV--Piog + Ang II group (Piog plus angiotensin II). mRNA and protein expression of collagen type I, III and angiotensin II type 1 receptor (AT1-R) were tested by reverse transcription--polymerase chain reaction and Western blotting. With the inhibition of actinomycin D, we investigated the impacts of Piog on the stability of AT1-RmRNA. Compared with group I, the mRNA and protein expression of collagen type I, III and AT1-R were up-regulated in group III (P < 0.05). However with the effects of Piog in group IV, the expressions mentioned above were attenuated significantly (P < 0.05). With the effects of actinomycin D, AT1-RmRNA was reduced at the same degree in control and Piog groups at the same time points. These results indicated that treatment with Piog can attenuate Ang II-induced collagen synthesis in CFs through down-regulation of the AT1-R expression. With the intervention of actinomycin D, we suggested that PPARgamma agonist didn't affect the stability of AT1-RmRNA.
Zhao
Shu-Mei
SM
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People's Republic of China.
Shen
Lu-Hua
LH
Li
Hong-Wei
HW
Wang
Lei
L
Chen
Hui
H
Wang
Yong-Ling
YL
Guo
Chun-Yan
CY
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D015536:Down-Regulation; D005347:Fibroblasts; D009206:Myocardium / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D020871:RNA Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D024042:Collagen Type I; D024061:Collagen Type III; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1