The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

作者全名："Song, Guangmin; Zhang, Dan; Zhu, Jianan; Wang, Andi; Zhou, Xiaobo; Han, Ting -Li; Zhang, Hua"

作者地址："[Song, Guangmin; Zhang, Dan; Zhu, Jianan; Wang, Andi; Zhou, Xiaobo; Zhang, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Song, Guangmin; Zhang, Dan; Zhu, Jianan; Zhou, Xiaobo; Zhang, Hua] Chongqing Med Univ, Canada China New Zealand Joint Lab Maternal & Feta, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Song, Guangmin; Zhang, Dan; Zhu, Jianan] Chongqing Key Lab Translat Med Major Metab Dis, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Han, Ting -Li] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynaecol, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Zhang, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, 1 Youyi Rd, Chongqing 400016, Peoples R China.; Han, TL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynaecol, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001176398600001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：CD73; Adenosine; Epithelial-mesenchymal transition; Energy metabolism; Extravillous trophoblast

摘要："The ecto-5 '-nucleotidase (CD73)/adenosine signaling pathway has been reported to regulate tumor epithelial-mesenchymal transition (EMT), migration and proliferation. However, little is known about the metabolic mechanisms underlying its role in trophoblast proliferation and migration. In this study, we aimed to investigate the metabolic role of the CD73/adenosine signaling pathway on the proliferation and migration of trophoblast. We found that CD73 levels were upregulated in preeclamptic placentas compared with the placentas of normotensive pregnant women. EMT and migration of HTR-8/SVneo cells were enhanced when treated with a CD73 inhibitor (100 mu M) in vitro. Conversely, excessive adenosine (25 or 50 mu M) suppressed trophoblast cell EMT, migration and proliferation. RNA-seq, metabolomics and seahorse findings showed that adenosine treatment resulted in increased expression of PDK1, suppression of aerobic respiration, glycolysis and amino acids synthesis, as well as increased utilization of short-chain fatty acids (SCFAs). Furthermore, the 13C-adenosine isotope tracking experiment demonstrated that adenosine served as a carbon source for the tricarboxylic acid (TCA) cycle. Our results reveal the role of adenosine in regulating trophoblast energy metabolism is like a double-edged sword either inhibiting aerobic respiration or supplementing carbon sources into metabolic flux. CD73/ adenosine signaling regulated trophoblast EMT, migration, and proliferation by modulating energy metabolism. This study indicates that CD73/adenosine signaling potentially plays a role in the occurrence of placenta-derived diseases, including preeclampsia."

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