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IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction

Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR...

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Autores principales: Zhang, Xin-Yan, Qin, Xue-Yun, Shen, Hui-Hui, Liu, Ke-Tong, Wang, Cheng-Jie, Peng, Ting, Wu, Jiang-Nan, Zhao, Shi-Min, Li, Ming-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969501/
https://www.ncbi.nlm.nih.gov/pubmed/36860682
http://dx.doi.org/10.7150/ijms.80684
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author Zhang, Xin-Yan
Qin, Xue-Yun
Shen, Hui-Hui
Liu, Ke-Tong
Wang, Cheng-Jie
Peng, Ting
Wu, Jiang-Nan
Zhao, Shi-Min
Li, Ming-Qing
author_facet Zhang, Xin-Yan
Qin, Xue-Yun
Shen, Hui-Hui
Liu, Ke-Tong
Wang, Cheng-Jie
Peng, Ting
Wu, Jiang-Nan
Zhao, Shi-Min
Li, Ming-Qing
author_sort Zhang, Xin-Yan
collection PubMed
description Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra(-/-) murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra(-/-) embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/β-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra(-/-) placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity. Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/β-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity.
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spelling pubmed-99695012023-02-28 IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction Zhang, Xin-Yan Qin, Xue-Yun Shen, Hui-Hui Liu, Ke-Tong Wang, Cheng-Jie Peng, Ting Wu, Jiang-Nan Zhao, Shi-Min Li, Ming-Qing Int J Med Sci Research Paper Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra(-/-) murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra(-/-) embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/β-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra(-/-) placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity. Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/β-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity. Ivyspring International Publisher 2023-02-05 /pmc/articles/PMC9969501/ /pubmed/36860682 http://dx.doi.org/10.7150/ijms.80684 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhang, Xin-Yan
Qin, Xue-Yun
Shen, Hui-Hui
Liu, Ke-Tong
Wang, Cheng-Jie
Peng, Ting
Wu, Jiang-Nan
Zhao, Shi-Min
Li, Ming-Qing
IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title_full IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title_fullStr IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title_full_unstemmed IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title_short IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction
title_sort il-27 deficiency inhibits proliferation and invasion of trophoblasts via the sfrp2/wnt/β-catenin pathway in fetal growth restriction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969501/
https://www.ncbi.nlm.nih.gov/pubmed/36860682
http://dx.doi.org/10.7150/ijms.80684
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