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SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

IN BRIEF: The establishment and maintenance of embryo implantation and pregnancy require decidualization of endometrial stromal cells. This paper reveals that SHP2 ensures the correct subcellular localization of progesterone receptor, thereby safeguarding the process of decidualization. ABSTRACT: De...

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Autores principales: Chen, Lin, Zhao, Weijie, Li, Mengxiong, Yang, Yazhu, Tian, Chengzi, Zhang, Dengyang, Chang, Zhiguang, Zhang, Yunzhe, Zhao, Zhizhuang Joe, Chen, Yun, Ma, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304905/
https://www.ncbi.nlm.nih.gov/pubmed/37184079
http://dx.doi.org/10.1530/REP-22-0367
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author Chen, Lin
Zhao, Weijie
Li, Mengxiong
Yang, Yazhu
Tian, Chengzi
Zhang, Dengyang
Chang, Zhiguang
Zhang, Yunzhe
Zhao, Zhizhuang Joe
Chen, Yun
Ma, Lin
author_facet Chen, Lin
Zhao, Weijie
Li, Mengxiong
Yang, Yazhu
Tian, Chengzi
Zhang, Dengyang
Chang, Zhiguang
Zhang, Yunzhe
Zhao, Zhizhuang Joe
Chen, Yun
Ma, Lin
author_sort Chen, Lin
collection PubMed
description IN BRIEF: The establishment and maintenance of embryo implantation and pregnancy require decidualization of endometrial stromal cells. This paper reveals that SHP2 ensures the correct subcellular localization of progesterone receptor, thereby safeguarding the process of decidualization. ABSTRACT: Decidualization is the process of conversion of endometrial stromal cells into decidual stromal cells, which is caused by progesterone production that begins during the luteal phase of the menstrual cycle and then increases throughout pregnancy dedicated to support embryonic development. Decidualization deficiency is closely associated with various pregnancy complications, such as recurrent miscarriage (RM). Here, we reported that Src-homology-2-containing phospho-tyrosine phosphatase (SHP2), a key regulator in the signal transduction process downstream of various receptors, plays an indispensable role in decidualization. SHP2 expression was upregulated during decidualization. SHP2 inhibitor RMC-4550 and shRNA-mediated SHP2 reduction resulted in a decreased level of phosphorylation of ERK and aberrant cytoplasmic localization of progesterone receptor (PR), coinciding with reduced expression of IGFBP1 and various other target genes of decidualization. Solely inhibiting ERK activity recapitulated these observations. Administration of RMC-4550 led to decidualization deficiency and embryo absorption in mice. Moreover, reduced expression of SHP2 was detected in the decidua of RM patients. Our results revealed that SHP2 is key to PR's nuclear localization, thereby indispensable for decidualization and that reduced expression of SHP2 might be engaged in the pathogenesis of RM.
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spelling pubmed-103049052023-06-29 SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor Chen, Lin Zhao, Weijie Li, Mengxiong Yang, Yazhu Tian, Chengzi Zhang, Dengyang Chang, Zhiguang Zhang, Yunzhe Zhao, Zhizhuang Joe Chen, Yun Ma, Lin Reproduction Research IN BRIEF: The establishment and maintenance of embryo implantation and pregnancy require decidualization of endometrial stromal cells. This paper reveals that SHP2 ensures the correct subcellular localization of progesterone receptor, thereby safeguarding the process of decidualization. ABSTRACT: Decidualization is the process of conversion of endometrial stromal cells into decidual stromal cells, which is caused by progesterone production that begins during the luteal phase of the menstrual cycle and then increases throughout pregnancy dedicated to support embryonic development. Decidualization deficiency is closely associated with various pregnancy complications, such as recurrent miscarriage (RM). Here, we reported that Src-homology-2-containing phospho-tyrosine phosphatase (SHP2), a key regulator in the signal transduction process downstream of various receptors, plays an indispensable role in decidualization. SHP2 expression was upregulated during decidualization. SHP2 inhibitor RMC-4550 and shRNA-mediated SHP2 reduction resulted in a decreased level of phosphorylation of ERK and aberrant cytoplasmic localization of progesterone receptor (PR), coinciding with reduced expression of IGFBP1 and various other target genes of decidualization. Solely inhibiting ERK activity recapitulated these observations. Administration of RMC-4550 led to decidualization deficiency and embryo absorption in mice. Moreover, reduced expression of SHP2 was detected in the decidua of RM patients. Our results revealed that SHP2 is key to PR's nuclear localization, thereby indispensable for decidualization and that reduced expression of SHP2 might be engaged in the pathogenesis of RM. Bioscientifica Ltd 2023-05-15 /pmc/articles/PMC10304905/ /pubmed/37184079 http://dx.doi.org/10.1530/REP-22-0367 Text en The Authors https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research
Chen, Lin
Zhao, Weijie
Li, Mengxiong
Yang, Yazhu
Tian, Chengzi
Zhang, Dengyang
Chang, Zhiguang
Zhang, Yunzhe
Zhao, Zhizhuang Joe
Chen, Yun
Ma, Lin
SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title_full SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title_fullStr SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title_full_unstemmed SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title_short SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor
title_sort shp2 participates in decidualization by activating erk to maintain normal nuclear localization of progesterone receptor
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304905/
https://www.ncbi.nlm.nih.gov/pubmed/37184079
http://dx.doi.org/10.1530/REP-22-0367
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