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CTHRC1 promotes growth, migration and invasion of trophoblasts via reciprocal Wnt/β-catenin regulation

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Preeclampsia (PE) is a pregnancy complication that is characterized by high blood pressure and is associated with high maternal and fetal morbidities. At a mechanistic level, PE is characterized by reduced invasion ability of trophoblasts. Collagen triple helix repeat containing-1 (CTHRC1) is a well-known tumor-promoting factor in several malignant tumors, but its role in trophoblasts remains unknown. In this study, we characterized the expression of CTHRC1 in placenta tissue samples from PE pregnancies and from normal pregnancies. We used the trophoblasts cell lines HTR-8/SVneo and JEG-3 to investigate the role of CTHRC1 in cell migration, invasion and proliferation. Western blot, PCR and TOP/FOP luciferase activity assays were used to investigate the molecular mechanisms underlying these cell behaviors. Placenta tissue samples obtained from pregnant women with PE expressed lower levels of CTHRC1 than those of placenta tissues from women with normal pregnancies. Down-regulation of CTHRC1 impaired cell proliferation, migration and invasion of trophoblasts, while CTHRC1 overexpression promoted nuclear translocation of β-catenin, a result that was further confirmed by TOP/FOP luciferase activity assay. Our findings suggest that CTHRC1 promotes migration and invasion of trophoblasts via reciprocal Wnt/β-catenin signaling pathway. Down-regulation of CTHRC1 may be a potential mechanism underpinning the development of preeclampsia.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, Shandong, China

    Yan Li, Bao-xiang Xing, Sha Yu, Han Zhao & Cai-xia Lu

  2. Department of Pain Medicine, Qingdao Municipal Hospital, 266011, Qingdao, Shandong, China

    Yi-hao Wang

  3. Department of Pathology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, Shandong, China

    Qing-qing Lv

  4. 16 Jiangsu Road, 266003, Qingdao, China

    Cai-xia Lu

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  1. Yan Li
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  5. Han Zhao
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Correspondence to Cai-xia Lu.

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Li, Y., Xing, Bx., Wang, Yh. et al. CTHRC1 promotes growth, migration and invasion of trophoblasts via reciprocal Wnt/β-catenin regulation. J. Cell Commun. Signal. 16, 63–74 (2022). https://doi.org/10.1007/s12079-021-00625-3

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