PlGF/FLT-1 deficiency leads to reduced STAT3-C/EBP beta signaling and aberrant polarization in decidual macrophages during early spontaneous abortion

作者全名："Chang, Ruiqi; Dai, Jingcong; Wang, Li; Liu, Hao; Jiang, Huanhuan; Liu, Xiaoyu; Jiang, Linying; He, Fan; Hu, Lina"

作者地址："[Chang, Ruiqi; He, Fan; Hu, Lina] Chongqing Med Univ, Ctr Reprod Med, Dept Obstet & Gynaecol, Affiliated Hosp 2, Chongqing, Peoples R China; [Chang, Ruiqi; He, Fan; Hu, Lina] Minist Educ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Chang, Ruiqi; He, Fan; Hu, Lina] Chongqing Med Univ, Reprod & Stem Cell Therapy Res Ctr Chongqing, Chongqing, Peoples R China; [Dai, Jingcong; Wang, Li; Liu, Hao; Jiang, Huanhuan; Liu, Xiaoyu; Jiang, Linying] Chongqing Med Univ, Dept Obstet & Gynaecol, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："He, F; Hu, LN (通讯作者)，Chongqing Med Univ, Ctr Reprod Med, Dept Obstet & Gynaecol, Affiliated Hosp 2, Chongqing, Peoples R China.; He, F; Hu, LN (通讯作者)，Minist Educ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China.; He, F; Hu, LN (通讯作者)，Chongqing Med Univ, Reprod & Stem Cell Therapy Res Ctr Chongqing, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000962889900001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：placental growth factor; Fms-like-tyrosine-kinase receptor 1; decidual stromal cells; decidual macrophage polarization; spontaneous abortion; early pregnancy

摘要："IntroductionDysregulated macrophage polarization (excessive M1-like or limited M2-like macrophages) in the early decidua contributes to allogeneic fetal rejection and thus early spontaneous abortion. However, the modulators of M1/M2 balance at the early maternal-fetal interface remain mostly unknown. MethodsFirst-trimester decidual tissues were collected from normal pregnant women undergoing elective pregnancy terminations and patients with spontaneous abortion. We measured the expression of placental growth factor (PlGF) and Fms-like-tyrosine-kinase receptor 1 (FLT-1), and characterized the profiles of macrophages in decidua. Notably, we investigated the effect of recombinant human PlGF (rhPlGF) on decidual macrophages (dM phi s) from normal pregnancy and revealed the underlying mechanisms both in vitro and in vivo. ResultsThe downregulated expression of PlGF/ FLT-1 may result in spontaneous abortion by inducing the M1-like deviation of macrophages in human early decidua. Moreover, the CBA/JxDBA/2 abortion-prone mice displayed a lower FLT-1 expression in uterine macrophages than did CBA/JxBALB/c control pregnant mice. In in vitro models, rhPlGF treatment was found to drive the M2-like polarization of dM phi s via the STAT3/CEBPB signaling pathway. These findings were further supported by a higher embryo resorption rate and uterine macrophage dysfunction in Pgf knockout mice, in addition to the reduced STAT3 transcription and C/EBP beta expression in uterine macrophages. DiscussionPlGF plays a key role in early pregnancy maintenance by skewing dM phi s toward an M2-like phenotype via the FLT-1-STAT3-C/EBP beta signaling pathway. Excitingly, our results highlight a rationale that PlGF is a promising target to prevent early spontaneous abortion."

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