CD55 被 cAMP/PKA/AKT 上调，并通过 Src 和 ERK 通路和蜕膜相关基因调节人类蜕膜,Molecular Reproduction and Development

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CD55 被 cAMP/PKA/AKT 上调，并通过 Src 和 ERK 通路和蜕膜相关基因调节人类蜕膜
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2022-04-26 , DOI: 10.1002/mrd.23569
Zhijing Tang _{1,

2} , Lu Wang ₁ , Zengshu Huang _{1,

2} , Haiyun Guan _{1,

2} , Wingting Leung _{1,

2} , Xiuying Chen ₁ , Hexia Xia ₁ , Wei Zhang ₁

Affiliation

蜕膜化是胚胎植入和维持妊娠的重要过程，异常蜕膜化会导致流产等多种妊娠疾病。本研究的目的是探讨 CD55 在人类蜕膜化中的调节和功能。通过免疫组织化学染色，发现CD55在妊娠早期蜕膜中的表达高于在子宫内膜中的表达。在原代子宫内膜基质细胞和永生化细胞系 T-hESCs 中，CD55 通过用醋酸甲羟孕酮 (MPA) 和 8-Br-cAMP 诱导体外蜕膜上调。在体外蜕膜化过程中，8-Br-cAMP 以时间和浓度依赖性方式刺激 CD55，而 PKA 抑制剂 H89 和部分 AKT 激活剂 SC79 可逆转 CD55。PRL ) 和胰岛素样生长因子结合蛋白 1 ( IGFBP1 )，伴随着 Src 的抑制、ERK 的异常激活和几个蜕膜相关基因的表达降低，包括FOXO1、EGFR和STAT3。此外，不明原因流产妇女的蜕膜和不明原因不孕妇女的子宫内膜均表现出CD55下降。表达。总的来说，这些研究结果表明 8-Br-cAMP 通过 PKA 激活和 AKT 去磷酸化促进 CD55 表达，并通过 Src 失活、ERK 通路异常激活和蜕膜相关基因表达受损来降低 CD55 损害蜕膜化，表明 CD55 缺乏可能有助于自然流产和不孕的发病机制。

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CD55 is upregulated by cAMP/PKA/AKT and modulates human decidualization via Src and ERK pathway and decidualization-related genes

Decidualization is an essential process for embryo implantation and maintenance of pregnancy, and abnormal decidualization contributed to several pregnancy disorders like a miscarriage. The objective of this study was to explore the regulation and function of CD55 in human decidualization. By immunohistochemical staining, it was found that CD55 expression was higher in first-trimester decidua than in the endometrium. In both primary endometrial stromal cells and immortalized cell line T-hESCs, CD55 was upregulated by induction of in vitro decidualization with medroxyprogesterone acetate (MPA) and 8-Br-cAMP. During decidualization in vitro, CD55 was stimulated by 8-Br-cAMP in a time- and concentration-dependent manner, which was reversed by a PKA inhibitor H89 and partially by an AKT activator SC79. Knocking down CD55 expression diminished the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1), accompanied by inhibition of Src, aberrant activation of ERK and decreased expression of several decidualization-related genes, including FOXO1, EGFR, and STAT3. Furthermore, the decidua of unexplained miscarriage women and the endometrium of unexplained infertile women both exhibited decreased CD55 expression. Collectively, these findings revealed that 8-Br-cAMP promotes CD55 expression via PKA activation and AKT dephosphorylation, and decreased CD55 impairs decidualization by inactivation of Src, aberrant activation of ERK pathway, and compromised expression of decidualization-related genes, indicating that CD55 deficiency may contribute to the pathogenesis of spontaneous miscarriage and infertility.

更新日期：2022-04-26

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