Cigarette smoke extract activates hypoxia-inducible factors in a reactive oxygen species-dependent manner in stroma cells from human endometrium

Naoko Kida, Yoshiyuki Matsuo, Yoshiko Hashimoto, Kenichiro Nishi, Tomoko Tsuzuki-Nakao, Hidemasa Bono, Tetsuo Maruyama, Kiichi Hirota, Hidetaka Okada

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number48
Pages (from-to)1-17
Number of pages17
JournalAntioxidants
Volume10
Issue number1
DOIs
Publication statusPublished - 2021 Jan

Keywords

  • Cigarette smoking
  • CS extract
  • Endometrial stromal cell
  • HIF
  • Hypoxia-inducible factor
  • Immortalized cell line
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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