HSP70 regulates lipid metabolism of decidual macrophages to maintain normal pregnancy

Yang, Dongyong; Dai, Fangfang; Wang, Linlin; Cai, Songchen; Zhang, Yuwei; Diao, Lianghui; Cheng, Yanxiang

doi:10.1016/j.jri.2023.103829

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…Maintenance of the macrophage phenotype and function requires energy provided by cellular metabolism. [ 30 , 46 ] Metabolic and functional changes in decidual macrophages at the maternal–fetal interface may play important roles in the development of RSA. Our untargeted metabolomic data revealed that JPT2‐deficient trophoblasts enhanced citrate production in macrophages.…”

Section: Discussionmentioning

confidence: 99%

JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion

Chen,

Song,

et al. 2024

Advanced Science

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Recurrent spontaneous abortion (RSA) is a pregnancy‐related condition with complex etiology. Trophoblast dysfunction and abnormal macrophage polarization and metabolism are associated with RSA; however, the underlying mechanisms remain unknown. Jupiter microtubule‐associated homolog 2 (JPT2) is essential for calcium mobilization; however, its role in RSA remains unclear. In this study, it is found that the expression levels of JPT2, a nicotinic acid adenine dinucleotide phosphate‐binding protein, are decreased in the villous tissues of patients with RSA and placental tissues of miscarried mice. Mechanistically, it is unexpectedly found that abnormal JPT2 expression regulates trophoblast function and thus involvement in RSA via c‐Jun N‐terminal kinase (JNK) signaling, but not via calcium mobilization. Specifically, on the one hand, JPT2 deficiency inhibits trophoblast adhesion, migration, and invasion by inhibiting the JNK/atypical chemokine receptor 3 axis. On the other hand, trophoblast JPT2 deficiency contributes to M1 macrophage polarization by promoting the accumulation of citrate and reactive oxygen species via inhibition of the JNK/interleukin‐6 axis. Self‐complementary adeno‐associated virus 9‐JPT2 treatment alleviates embryonic resorption in abortion‐prone mice. In summary, this study reveals that JPT2 mediates the remodeling of the immune microenvironment at the maternal–fetal interface, suggesting its potential as a therapeutic target for RSA.

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Section: Discussionmentioning

confidence: 99%

JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion

Chen,

Song,

et al. 2024

Advanced Science

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“…Some parental genes of dysregulated circRNAs are enriched in the interleukin-6/type I interferon, T-helper 17 cell differentiation and T-cell receptor-related signaling pathways (Figure 2D), which are significant in the maintenance of maternal-fetal tolerance. Metabolic disorders are also related to RPL [28,29], but the underlying mechanisms thereof have not been clarified clearly. The parental genes of dysregulated circRNAs are enriched in metabolic pathways, such as those that are pyruvate-, lipid-and glucose-related.…”

Section: Go and Kegg Pathway Analyses Of Parental Genes Of Differenti...mentioning

confidence: 99%

Identification of m6A Modification Regulated by Dysregulated circRNAs in Decidua of Recurrent Pregnancy Loss

Cui,

Shi,

Meng

et al. 2023

CIMB

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N6-methyladenosine (m6A) modification is a prevalent modification of messenger ribonucleic acid (mRNA) in eukaryote cells and is closely associated with recurrent pregnancy loss (RPL). Circular RNAs (circRNAs) play critical roles in embryo implantation, trophoblast invasion and immune balance, which are important events during pregnancy. However, how m6A modification is regulated by circRNAs and the potential regulatory mechanism of circRNAs on RPL occurrence remain largely unclassified. We displayed the expression profiles of circRNAs and mRNAs in the decidua of normal pregnancies and RPL patients based on circRNA sequencing and the Gene Expression Omnibus database. A total of 936 differentially expressed circRNAs were identified, including 509 upregulated and 427 downregulated circRNAs. Differentially expressed circRNAs were enriched in immune, metabolism, signaling and other related pathways via the analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The competitive endogenous RNA (ceRNA) network was predicted to supply the possible role of circRNAs in RPL occurrence, and we further analyzed the profiles of nine m6A regulators (seven readers, one writer and one eraser) managed by circRNAs in this network. We also showed the expression profiles of circRNAs in the serum, trying to seek a potential biomarker to help in the diagnosis of RPL. These data imply that circRNAs are involved in pathogenesis of RPL by changing immune activities, metabolism and m6A modification in the ceRNA network. Our study might provide assistance in exploring the pathogenesis and diagnosis of RPL.

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FKBP5 regulates trophoblast-macrophage crosstalk in recurrent spontaneous abortion through PI3K/AKT and NF-κB signaling pathways

Chen,

Song,

Wang

et al. 2023

Free Radical Biology and Medicine

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HSP70 regulates lipid metabolism of decidual macrophages to maintain normal pregnancy

Cited by 4 publications

References 35 publications

JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion

JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion

Identification of m6A Modification Regulated by Dysregulated circRNAs in Decidua of Recurrent Pregnancy Loss

FKBP5 regulates trophoblast-macrophage crosstalk in recurrent spontaneous abortion through PI3K/AKT and NF-κB signaling pathways

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