Kida Naoko, Matsuo Yoshiyuki, Hashimoto Yoshiko, Nishi Kenichiro, Tsuzuki-Nakao Tomoko, Bono Hidemasa, Maruyama Tetsuo, Hirota Kiichi, Okada Hidetaka
Department of Obstetrics and Gynecology, Kansai Medical University, 2-3-1 shinmachi-cho, Hirakata 573-1191, Japan.
Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan.
Antioxidants (Basel). 2021 Jan 3;10(1):48. doi: 10.3390/antiox10010048.
Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.
吸烟是导致大量致命和使人衰弱疾病（包括退行性疾病和癌症）的主要因素。吸烟和被动吸烟也会影响妊娠的建立和维持。然而，据我们所知，吸烟对人体子宫内膜的影响仍知之甚少。在本研究中，我们使用原代人子宫内膜基质细胞和永生化细胞系（KC02-44D）研究了吸烟诱导缺氧诱导因子（HIF）-1α激活的调控机制。我们发现，香烟提取物（CSE）可增加子宫内膜基质细胞中的活性氧水平，并刺激HIF-1α蛋白稳定，且在非缺氧条件下，香烟诱导的HIF-1α依赖性基因表达呈浓度和时间依赖性。此外，我们还发现，即使在常氧条件下，CSE处理后缺氧诱导基因集的表达也会上调。这些结果表明，HIF-1α可能在吸烟暴露诱导的细胞应激、炎症和子宫内膜重塑中起重要作用。
