Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2(+) macrophage differentiation.
Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2(+) macrophage differentiation.
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1,6-二磷酸果糖通过诱导蜕膜 COX-2( ) 巨噬细胞分化来预防妊娠流产。
DOI：
10.1126/sciadv.abj2488
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发表时间：
2022-02-25
期刊：
影响因子：
13.6
通讯作者：
Li MQ
中科院分区：
文献类型：
--
作者：
Zhou WJ;Yang HL;Mei J;Chang KK;Lu H;Lai ZZ;Shi JW;Wang XH;Wu K;Zhang T;Wang J;Sun JS;Ye JF;Li DJ;Zhao JY;Jin LP;Li MQ
蜕膜化是一个复杂的生物学过程，其中子宫内膜发生广泛的重塑以支持着床胚泡的发育。然而，这一过程背后的免疫代谢机制在很大程度上仍然是未知的。我们发现，蜕膜化过程伴随着果糖-1，6-二磷酸（FBP）的积累。FBP与丙酮酸激酶M的组合以ERK/c-FOS依赖的方式刺激子宫内膜间质细胞分泌IL-27。IL-27诱导蜕膜考克斯-2 + M2样巨噬细胞分化，促进蜕膜化、滋养层浸润和母胎耐受。转移Ptgs 2 +/考克斯-2+巨噬细胞可防止Il27 ra缺失的妊娠小鼠的胎儿丢失。不明原因反复自然流产患者血浆和蜕膜组织中的FBP水平较低。在治疗研究中，在自然流产小鼠模型中，补充FBP通过上调IL-27诱导的考克斯-2+巨噬细胞分化显著改善胚胎丢失。这些发现共同为预防妊娠丢失的潜在治疗策略提供了科学依据。果糖-1，6-二磷酸/IL-27/考克斯-2 + M2-样蜕膜巨噬细胞轴失衡导致流产。
Decidualization is an intricate biological process in which extensive remodeling of the endometrium occurs to support the development of an implanting blastocyst. However, the immunometabolic mechanisms underlying this process are still largely unknown. We found that the decidualization process is accompanied by the accumulation of fructose-1,6-bisphosphate (FBP). The combination of FBP with pyruvate kinase M stimulated IL-27 secretion by endometrial stromal cells in an ERK/c-FOS–dependent manner. IL-27 induced decidual COX-2+ M2-like macrophage differentiation, which promotes decidualization, trophoblast invasion, and maternal-fetal tolerance. Transfer of Ptgs2+/COX-2+ macrophages prevented fetal loss in Il27ra-deleted pregnant mice. FBP levels were low in plasma and decidual tissues of patients with unexplained recurrent spontaneous abortion. In therapeutic studies, FBP supplementation significantly improved embryo loss by up-regulation of IL-27–induced COX-2+ macrophage differentiation in a mouse model of spontaneous abortion. These findings collectively provide a scientific basis for a potential therapeutic strategy to prevent pregnancy loss. Imbalance in the fructose-1,6-bisphosphate/IL-27/COX-2+ M2-like decidual macrophage axis leads to miscarriage.
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影响因子：
3.7
作者：
Lee CH;Kim TH;Lee JH;Oh SJ;Yoo JY;Kwon HS;Kim YI;Ferguson SD;Ahn JY;Ku BJ;Fazleabas AT;Lim JM;Jeong JW
通讯作者：
Jeong JW
影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
影响因子：
--
作者：
Frolova, Antonina I.;O'Neill, Kathleen;Moley, Kelle H.
通讯作者：
Moley, Kelle H.
DOI：
10.1111/aji.12473
发表时间：
2016-03
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Bhurke AS;Bagchi IC;Bagchi MK
通讯作者：
Bagchi MK
影响因子：
16
作者：
Lee JH;Liu R;Li J;Wang Y;Tan L;Li XJ;Qian X;Zhang C;Xia Y;Xu D;Guo W;Ding Z;Du L;Zheng Y;Chen Q;Lorenzi PL;Mills GB;Jiang T;Lu Z
通讯作者：
Lu Z