Deficiency of cold-inducible RNA-binding protein exacerbated monocrotaline-induced pulmonary artery hypertension through Caveolin1 and CAVIN1.
Deficiency of cold-inducible RNA-binding protein exacerbated monocrotaline-induced pulmonary artery hypertension through Caveolin1 and CAVIN1.
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冷诱导 RNA 结合蛋白的缺乏会通过 Caveolin1 和 CAVIN1 加剧野百合碱诱导的肺动脉高压。
DOI：
10.1111/jcmm.16437
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Liu J;Ke X;Wang L;Zhang Y;Yang J
冷诱导RNA结合蛋白(CIRP)是多种疾病的重要调节因子。然而，它在肺动脉高压(PAH)中的作用仍不清楚。我们首先建立了野百合碱(MCT)诱导的大鼠PAH模型，发现注射MCT后，CIRP主要在肺血管内皮细胞表达下调。然后，我们建立了CIRP基因敲除(CIRP-KO)大鼠，作为对MCT的反应，大鼠表现出更严重的PAH和加重的内皮损伤。随后，Caveolin1(Cav1)和Cavin1被确定为MCT诱导的PAH中CIRP的下游靶点，这两个基因的表达减少加剧了肺动脉内皮细胞的损伤和凋亡。此外，CIRP缺乏加重了野百合碱吡咯(MCTP)诱导的大鼠肺动脉内皮细胞(RPAECs)在体内和体外的损伤，Cav1或Cavin1过表达可拮抗该损伤。此外，CIRP还可调节MCTP处理的rPAECs条件培养液对大鼠肺动脉平滑肌细胞的增殖作用，这部分解释了MCT处理后CIRP-KO大鼠肺动脉内膜过度增厚的原因。这些结果表明，CIRP通过直接调节CAV1和CAVIN1的表达，在MCT诱导的大鼠PAH中发挥重要的保护作用，这可能有助于开发干预PAH的新的治疗靶点。
Cold‐inducible RNA‐binding protein (CIRP) was a crucial regulator in multiple diseases. However, its role in pulmonary artery hypertension (PAH) is still unknown. Here, we first established monocrotaline (MCT)‐induced rat PAH model and discovered that CIRP was down‐regulated predominantly in the endothelium of pulmonary artery after MCT injection. We then generated Cirp‐knockout (Cirp‐KO) rats, which manifested severer PAH with exacerbated endothelium damage in response to MCT. Subsequently, Caveolin1 (Cav1) and Cavin1 were identified as downstream targets of CIRP in MCT‐induced PAH, and the decreased expression of these two genes aggravated the injury and apoptosis of pulmonary artery endothelium. Moreover, CIRP deficiency intensified monocrotaline pyrrole (MCTP)‐induced rat pulmonary artery endothelial cells (rPAECs) injuries both in vivo and in vitro, which was counteracted by Cav1 or Cavin1 overexpression. In addition, CIRP regulated the proliferative effect of conditioned media from MCTP‐treated rPAECs on rat pulmonary artery smooth muscle cells, which partially explained the exceedingly thickened pulmonary artery intimal media in Cirp‐KO rats after MCT treatment. These results demonstrated that CIRP acts as a critical protective factor in MCT‐induced rat PAH by directly regulating CAV1 and CAVIN1 expression, which may facilitate the development of new therapeutic targets for the intervention of PAH.
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影响因子：
4
作者：
Sowa G
通讯作者：
Sowa G
冷诱导的 RNA 结合蛋白通过控制选择性多聚腺苷酸化来调节昼夜节律基因表达
影响因子：
4.6
作者：
Liu, Yuting;Hu, Wenchao;Murakawa, Yasuhiro;Yin, Jingwen;Wang, Gang;Landthaler, Markus;Yan, Jun
通讯作者：
Yan, Jun
DOI：
10.5320/wjr.v5.i2.126
发表时间：
2015-07-28
期刊：
World journal of respirology
影响因子：
--
作者：
Chettimada S;Yang J;Moon HG;Jin Y
通讯作者：
Jin Y
DOI：
10.1007/978-1-61779-191-8_21
发表时间：
2011-01-01
期刊：
PERMEABILITY BARRIER: METHODS AND PROTOCOLS
影响因子：
--
作者：
Sun, Yu;Minshall, Richard D.;Hu, Guochang
通讯作者：
Hu, Guochang
影响因子：
4.8
作者：
Schubert, W;Frank, PG;Lisanti, MP
通讯作者：
Lisanti, MP