EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-beta 1 signaling
文献类型：期刊论文
| 作者 | Lu, Ankang; Zuo, Caojian; He, Yuhu; Chen, Guilin; Piao, Lingjuan; Zhang, Jian; Xiao, Bing; Shen, Yujun; Tang, Juan; Kong, Deping |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2015 |
| 卷号 | 125期号:3页码:1228-1242 |
| 英文摘要 | Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3 alpha and EP3 beta, but not EP3 gamma, isoforms diminished hypoxia-induced TGF-beta 1 activation. Expression of either EP3 alpha or EP3 beta in EP3-deficient PASMCs restored TGF-beta 1 activation in response to hypoxia. EP3 alpha/beta activation in PASMCs increased RhoA-dependent membrane type1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro-MMP-2 and promoting TGF-beta 1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension. |
| 类目[WOS] | Medicine, Research & Experimental |
| 研究领域[WOS] | Research & Experimental Medicine |
| 关键词[WOS] | GROWTH-FACTOR-BETA ; BONE MORPHOGENETIC PROTEIN ; RHO-KINASE INHIBITOR ; SMOOTH-MUSCLE-CELLS ; ARTERIAL-HYPERTENSION ; PROSTANOID RECEPTORS ; PROSTACYCLIN ANALOGS ; MATRIX-METALLOPROTEINASE ; PROSTAGLANDIN RECEPTORS ; EXTRACELLULAR-MATRIX |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000350616500035 |
| 公开日期 | 2015-09-08 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/134]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_核受体与代谢和疾病研究组 中国科学院上海生命科学研究院营养科学研究所_磷脂代谢与心血管疾病研究组 中国科学院上海生命科学研究院营养科学研究所_心脏发育与再生研究组 |
| 推荐引用方式 GB/T 7714 | Lu, Ankang,Zuo, Caojian,He, Yuhu,et al. EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-beta 1 signaling[J]. JOURNAL OF CLINICAL INVESTIGATION,2015,125(3):1228-1242. |
| APA | Lu, Ankang.,Zuo, Caojian.,He, Yuhu.,Chen, Guilin.,Piao, Lingjuan.,...&Yu, Ying.(2015).EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-beta 1 signaling.JOURNAL OF CLINICAL INVESTIGATION,125(3),1228-1242. |
| MLA | Lu, Ankang,et al."EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-beta 1 signaling".JOURNAL OF CLINICAL INVESTIGATION 125.3(2015):1228-1242. |
入库方式： OAI收割
来源：上海营养与健康研究所
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