Down-Regulation of the Expression of Angiotensin Ⅱ Type 1 Receptor in Neonatal Rat Cardiac Fibroblast by Activation of PPARγ Signal Pathway

Shu-Mei Zhao；Lu-Hua Shen；Hong-Wei Li；Lei Wang；Hui Chen；Yong-Ling Wang；Chun-Yan Guo

PPARγ agonist ； cardiac fibrosis ； angiotensin Ⅱ type 1 receptor ； actinomycin D

The Chinese Journal of Physiology

51卷6期（2008 / 12 / 01）

357 - 362

英文

Peroxisome proliferator-activated receptor-gamma (PPARγ) is one of the hormone nuclear receptors. Recent data have shown that activation of PPARγ signal pathway has many positive effects on cardiovascular system. The goals of this study were to determine whether PPARγ 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-PPARγ 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 PPARγ agonist didn't affect the stability of AT1-RmRNA.

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