TY - JOUR
T1 - Cigarette smoke extract activates hypoxia-inducible factors in a reactive oxygen species-dependent manner in stroma cells from human endometrium
AU - Kida, Naoko
AU - Matsuo, Yoshiyuki
AU - Hashimoto, Yoshiko
AU - Nishi, Kenichiro
AU - Tsuzuki-Nakao, Tomoko
AU - Bono, Hidemasa
AU - Maruyama, Tetsuo
AU - Hirota, Kiichi
AU - Okada, Hidetaka
N1 - Funding Information:
Funding: This work was supported by the Japan Society for the Promotion of Science KAKENHI (grants JP20K09210 and JP20K09210 to K.N., Y.M., and K.H.; and JP19K09766 to T.T.-N.). This work was also supported by a research grant from the Kansai Medical University (KMU) research consortium to K.H., the branding program as a world-leading research university on intractable immune and allergic diseases from MEXT Japan.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - CS extract
KW - Cigarette smoking
KW - Endometrial stromal cell
KW - HIF
KW - Hypoxia-inducible factor
KW - Immortalized cell line
KW - Reactive oxygen species
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U2 - 10.3390/antiox10010048
DO - 10.3390/antiox10010048
M3 - Article
AN - SCOPUS:85099409971
VL - 10
SP - 1
EP - 17
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 1
M1 - 48
ER -