2024-03-19T13:00:05Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00023041
2023-01-16T05:05:53Z
499:500:501
Progestin isoforms provide different levels of protein S expression in HepG2 cells
Kozuka, Toshihiro
Tamura, Shogo
Kawamura, Nami
Nakata, Yukiko
Hasebe, Ryo
Makiyama, Ayumi
Takagi, Yuki
Murata, Moe
Mizutani, Naoki
Takagi, Akira
Kojima, Tetsuhito
open access
© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Protein S
Progestin
Transcription elongation
Combined oral contraceptive
Venous thromboembolism
Introduction: Use of combined oral contraceptives (COCs) results in acquired protein S (PS) deficiency, a well-established risk factor for venous thromboembolism (VTE). The risk of VTE due to COCs containing newer-generation progestins is double compared with COCs containing older-generation progestins, although there is little difference in estrogen contents between the generations. In contrast, progestin-only contraceptives do not confer an increased risk of VTE. In this study, we aimed to investigate how different isoforms of progestin in COCs affect the risk of VTE by measuring PS expression. Materials and methods: The effect of progestin, levonorgestrel (LNG) or drospirenone (DRSP), on PS mRNA expression in HepG2 cells was measured using reverse transcription-quantitative PCR; PS level was determined using Western blot analysis. PROS1 promoter activity, PS mRNA stability, and de novo synthesis of PS mRNA were examined in HepG2 cells after treatment with progestin. Results and conclusions: In the presence of progestins, PS mRNA and protein expressions were significantly upregulated in HepG2 cells due to the augmentation of de novo PS mRNA expression modulated by RNA polymerase II (Pol II), thereby facilitating PS transcription elongation. Moreover, the transcription elongation inhibitor blocked progestin-mediated de novo PS mRNA expression. Conversely, progestin did not affect PROS1 promoter activity and PS mRNA stability. Pol II elongation efficiency in the newer-generation progestin (DRSP) treatment was not as strong compared with older-generation progestin (LNG), suggesting the difference in VTE risk between COC generations.
Elsevier
2016-09
eng
journal article
AM
http://hdl.handle.net/2237/25229
https://nagoya.repo.nii.ac.jp/records/23041
https://doi.org/10.1016/j.thromres.2016.07.007
0049-3848
Thrombosis Research
145
40
45
https://nagoya.repo.nii.ac.jp/record/23041/files/Progestin_PS_Rv3_kozuka.pdf
application/pdf
775.3 kB
2017-09-01