Mice lacking 1,4,5-triphosphate inositol type III receptor demonstrate inhibition of hypoxic pulmonary hypertension.
Mice lacking 1,4,5-triphosphate inositol type III receptor demonstrate inhibition of hypoxic pulmonary hypertension.
复制标题
缺乏 1,4,5-三磷酸肌醇 III 型受体的小鼠表现出对缺氧性肺动脉高压的抑制作用。
DOI：
10.1016/j.bbrc.2022.09.036
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发表时间：
2022
影响因子：
3.1
通讯作者：
Yupeng Yin
中科院分区：
文献类型：
--
作者：
Xinyue Guo;Yinan Meng;Yumiao Wang;Shifa Nan;Yuchen Lu;Dezhang Lu;Yupeng Yin
低血压性肺动脉高压（HPH）是一种以肺血管阻力和肺动脉压增加为特征的呼吸系统疾病。持续缺氧改变了内皮细胞的代谢和运输功能，并促进血栓形成和炎症。3型肌醇-1，4，5-三磷酸受体（IP 3R 3）控制钙离子从内质网释放到细胞质和线粒体，并参与细胞增殖、迁移和蛋白质合成。在本研究中，我们研究了IP 3R 3在HPH中的作用和功能。结果表明，在大鼠HPH模型中，IP 3R 3在肺动脉内皮细胞（PAECs）中的表达水平增加。持续缺氧的IP 3R 3（−/−）小鼠的肺动脉压指数显著低于HPH小鼠。IP 3R 3的表达水平在缺氧处理的PAEC中显著增加。IP 3R 3基因的敲低可显著抑制缺氧诱导的PAECs增殖、迁移和间质转化。总之，IP 3R 3的敲低可以抑制PAEC中缺氧诱导的功能障碍，从而使IP 3R 3（−/−）小鼠能够避免HPH的发展。IP 3R 3在HPH中起关键作用，可作为HPH预防和治疗的潜在靶点。
Hypoxic pulmonary hypertension (HPH) is a respiratory disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. Persistent hypoxia alters the metabolic and transport functions of endothelial cells and promotes thrombosis and inflammation. Type 3 inositol-1,4,5-trisphosphate receptor (IP3R3) controls the release of calcium ions from the endoplasmic reticulum to the cytoplasm and mitochondria and is involved in cell proliferation, migration, and protein synthesis. In this study, we investigated the role and function of IP3R3 in HPH. The results showed that the expression level of IP3R3 was increased in pulmonary artery endothelial cells (PAECs) in a rat HPH model. The pulmonary artery pressure indices of IP3R3(−/−)mice with persistent hypoxia were significantly lower than those of HPH mice. The expression level of IP3R3 was significantly increased in hypoxia-treated PAECs. Knockdown of IP3R3 significantly inhibited the proliferation, migration and mesenchymal transition of PAECs induced by hypoxia. In conclusion, knockdown of IP3R3 can inhibit hypoxia-induced dysfunctions in PAECs, thus enabling IP3R3(−/−)mice to avoid HPH development. IP3R3 plays a key role in HPH and can be used as a potential target for the prevention and treatment of HPH.
影响因子：
4
作者：
Gabani, Mohanad;Liu, Jing;Kassan, Modar
通讯作者：
Kassan, Modar