Institute of Respiratory Medicine, Hunan Province Geriatric Hospital, Changsha, Hunan 410016, P.R. China.
Int J Mol Med. 2015 Jul;36(1):271-81. doi: 10.3892/ijmm.2015.2209. Epub 2015 May 14.
Pulmonary hypertension (PH) develops in 30-70% of chronic obstructive pulmonary disease patients and increases morbidity and mortality. The present study aimed to investigate the regulation of small ubiquitin‑related modifier‑1 (SUMO‑1) expression in response to hypoxia. The experiments were carried out in vitro in rat pulmonary arterial smooth muscle cells (PASMCs) and in vivo using a rat hypoxic PH (HPH) model. A significant increase in SUMO‑1 mRNA and protein levels was observed following hypoxic stimulation in vivo and in vitro. SUMO‑1 is known to interact with various transcription factors, including hypoxia‑inducible factor‑1α (HIF‑1α) in vitro. Notably, the expression of HIF‑1α and its target gene, vascular endothelial growth factor, was increased by hypoxia in HPH. In addition, the present data suggest that SUMO‑1 regulated HIF‑1α in response to hypoxia (gene silencing and overexpression). Finally, the co‑immunoprecipitation assays suggest a direct and specific interaction between SUMO‑1 and HIF‑1α. In conclusion, SUMO‑1 may participate in the modulation of HIF‑1α through sumoylation in HPH. However, further studies are required to confirm this.
肺高血压（PH）在 30-70%的慢性阻塞性肺疾病患者中发展，并增加发病率和死亡率。本研究旨在研究小泛素相关修饰物-1（SUMO-1）表达对缺氧的调节。该实验在体外大鼠肺动脉平滑肌细胞（PASMCs）和体内大鼠低氧性 PH（HPH）模型中进行。在体内和体外缺氧刺激后，观察到 SUMO-1 mRNA 和蛋白水平显著增加。SUMO-1 已知与各种转录因子相互作用，包括体外缺氧诱导因子-1α（HIF-1α）。值得注意的是，HIF-1α及其靶基因血管内皮生长因子的表达在 HPH 中因缺氧而增加。此外，本数据表明 SUMO-1 通过基因沉默和过表达来调节缺氧反应中的 HIF-1α。最后，共免疫沉淀实验表明 SUMO-1 和 HIF-1α之间存在直接和特异性相互作用。总之，SUMO-1 可能通过 HPH 中的 SUMO 化参与 HIF-1α的调节。然而，需要进一步的研究来证实这一点。
