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首页> 外文期刊>Cell metabolism >PPAR gamma Links BMP2 and TGF beta 1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism
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PPAR gamma Links BMP2 and TGF beta 1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism

机译:PPARγ链接BMP2和TGFβ1血管平滑肌细胞的途径,调节细胞增殖和葡萄糖代谢

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摘要

BMP2 and TGF beta 1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in VSMCs, and their disturbance in pulmonary arterial hypertension (PAH), are unclear. We found a pro-proliferative TGF beta 1-Stat3-FoxO1 axis in VSMCs, and PPAR gamma as inhibitory regulator of TGF beta 1-Stat3-FoxO1 and TGF beta 1-Smad3/4, by physically interacting with Stat3 and Smad3. TGF beta 1 induces fibrosis-related genes and miR-130a/301b, suppressing PPAR gamma. Conversely, PPAR gamma inhibits TGF beta 1-induced mitochondrial activation and VSMC proliferation, and regulates two glucose metabolism-related enzymes, platelet isoform of phosphofructokinase (PFKP, a PPAR gamma target, via miR-331-5p) and protein phosphatase 1 regulatory subunit 3G (PPP1R3G, a Smad3 target). PPAR gamma knockdown/deletion in VSMCs activates TGF beta 1 signaling. The PPAR gamma agonist pioglitazone reverses PAH and inhibits the TGF beta 1-Stat3-FoxO1 axis in TGF beta 1-overexpressing mice. We identified PPAR gamma as a missing link between BMP2 and TGF beta 1 pathways in VSMCs. PPAR gamma activation can be beneficial in TGF beta 1-associated diseases, such as PAH, parenchymal lung diseases, and Marfan's syndrome.
机译:BMP2和TGFβ1是动脉,心脏和肺中病理重塑的功能性拮抗剂;然而,VSMC中的机制及其对肺动脉高血压(PAH)的干扰尚不清楚。我们在VSMCS中发现了一种促进的TGFβ1-STAT3-FOXO1轴,通过与Stat3和SMAD3的物理相互作用,通过物理地相互作用,在VSMCS中以VSMCS和PPARγ作为TGFβ1-STAT3-FOXO1和TGFβ1-SMAD3 / 4的抑制稳定剂。 TGFβ1诱导纤维化相关基因和miR-130a / 301b,抑制PPARγ。相反,PPARγ抑制TGFβ1诱导的线粒体激活和VSMC增殖,并调节两个葡萄糖代谢相关酶,磷酸荧光蛋白酶(PFKP,PPARγ靶,通过MIR-331-5P)和蛋白质磷酸酶1调节亚基的血小板同种型3G(PPP1R3G,SMAD3目标)。 VSMCS中的PPAR Gamma击倒/删除激活TGF Beta 1信令。 PPARγ激动剂Pioglitazone反转PAH并抑制TGFβ1-过度抑制小鼠中的TGFβ1-STAT3-FOXO1轴。我们将PPAR GAMMA识别为VSMC中BMP2和TGF Beta 1路径之间的缺失链接。 PPARγ活化可以有益于TGFβ1-相关疾病,如PAH,实体肺病和Marfan的综合症。

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  • 来源
    《Cell metabolism》 |2017年第5期|共24页
  • 作者单位

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

    Hannover Med Sch Inst Pathol D-30625 Hannover Germany;

    Semmelweis Univ Dept Pathophysiol H-1089 Budapest Hungary;

    Hannover Med Sch Dept Pediat Cardiol &

    Crit Care D-30625 Hannover Germany;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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