PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPARγ in cardiac fibroblasts (Publication with Expression of Concern. See vol. 117, pg. 2822, 2021)
PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPARγ in cardiac fibroblasts (Publication with Expression of Concern. See vol. 117, pg. 2822, 2021)
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DOI：
10.1093/cvr/cvn264
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发表时间：
2009-01-01
影响因子：
10.8
通讯作者：
Huang, Kai
中科院分区：
文献类型：
--
作者：
Huang, Dan;Yang, Chongzhe;Huang, Kai
为探讨脂联素及其受体（AdipoR）在体外培养的大鼠心肌成纤维细胞中的转录调控机制，采用Western blot和实时荧光定量RT-PCR方法检测了脂联素及其受体在心肌成纤维细胞中的表达。用Southwestern印迹法和电泳迁移率变动分析法测定了过氧化物酶体增殖物激活受体γ（PPAR γ）的DNA结合活性。结果显示，脂联素和AdipoR 1在体外培养的大鼠心脏成纤维细胞中高表达。通过3-氨基苯甲酰胺、PJ 34或PARP-1 siRNA抑制聚（ADP-核糖）聚合酶1（PARP-1）可显著增加培养的成纤维细胞、成熟3 T3 L1脂肪细胞、大鼠心肌和白色脂肪组织中脂联素和AdipoR 1的转录。在基础条件下，心脏成纤维细胞中的PARP-1使PPAR γ聚（ADP-核糖基）化。PPARgamma的聚（ADP-核糖基）化阻止其与DNA结合。PARP-1的抑制增强了DNA结合和PPAR γ的反式激活，并增加了培养的成纤维细胞中的PPAR γ靶基因（包括CD 36、脂蛋白脂肪酶和leptin）的转录。PARP-1抑制了培养的大鼠心脏成纤维细胞中脂联素和AdipoR 1的表达，并通过多聚（ADP-核糖基）化抑制了PPAR γ的反式激活。
Our aim was to explore the mechanism underlying the transcriptional regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac fibroblasts.Using western blot and real-time RT-PCR assays, the expression of adiponectin and its receptors was determined. Using Southwestern blot and electrophoretic mobility shift assays, the DNA binding activity of peroxisome proliferator activated receptor gamma (PPAR gamma) was determined. The results showed that adiponectin and AdipoR1 were highly expressed in cultured rat cardiac fibroblasts. Inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) by 3-aminobenzamide, PJ34, or PARP-1 siRNA markedly increased the transcription of adiponectin and AdipoR1 in cultured fibroblasts, mature 3T3 L1 adipocytes, rat myocardium, and white adipose tissue. PPAR gamma was poly(ADP-ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP-ribosyl)ation of PPAR gamma prevented its binding to DNA. Inhibition of PARP-1 enhanced the DNA binding and transactivation of PPAR gamma and increased the transcription of PPAR gamma-target genes including CD36, lipoprotein lipase, and leptin in cultured fibroblasts.PARP-1 inhibits adiponectin and AdipoR1 expression as well as PPAR gamma transactivation through poly(ADP-ribosyl)ation of PPAR gamma in cultured rat cardiac fibroblasts.