Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy

Marchetto, Nicole M.; Begum, Salma; Wu, Tracy; O'Besso, Valerie; Yarborough, Christina C.; Valero-Pacheco, Nuriban; Beaulieu, Aimee M.; Kitajewski, Jan; Shawber, Carrie J.; Douglas, Nataki C.

doi:10.3390/ijms21186477

Cited by 11 publications

(16 citation statements)

References 59 publications

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“…In response to blastocyst implantation, the endometrium experiences stromal-decidual transformation to provide an appropriate environment for the growing conceptus [38,39]. Plentiful researches have been carried out regarding the involvement of Notch signaling in the uterus during early pregnancy [27][28][29][40][41][42]. In our previous study, we uncovered dual roles of Rbpj, the nuclear…”

Section: Discussionmentioning

confidence: 99%

Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2

et al. 2021

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The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.

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Section: Discussionmentioning

confidence: 99%

Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2

et al. 2021

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“…Previous reports have suggested that Dll4 and Jagged1 play an important role in angiogenesis. Marchetto et al revealed that endothelial Jagged1 antagonizes Dll4/Notch signaling in decidual angiogenesis during early mouse pregnancy [ 24 ]. Oon suggested the role of Dll4 in Jagged1-induced tumor angiogenesis and tumor growth [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model

et al. 2021

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Retinopathy of Prematurity (ROP), a type of retinal neovascularization in premature infants, has become a serious problem that drastically affects the quality of life of premature infants. ROP is associated with angiogenesis and neovascularization. Here, we aimed to explain the function and latent roles of Cytochrome P450 2J2 (CYP2J2) in hypoxia-induced retinopathy in retinal vascular endothelial cells (HRVECs). HRVECs were stimulated with hypoxia for 24 h to establish an in vitro retinopathy model. Cell viability and migration were evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Protein and gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. We observed that pcDNA3.1(+)-CYP2J2 promoted CYP2J2 and Jagged1 expression, while Dll4 was down-regulated in hypoxia-stimulated HRVECs. Additionally, pcDNA3.1(+)-CYP2J2 inhibited HRVEC viability, reduced PCNA expression, and inhibited the migration of HRVECs. Further, the Notch pathway was inhibited in the Hypoxia+pcDNA3.1(+)-CYP2J2 group. Opposite results were observed upon Terfenadone treatment in hypoxia induced HRVECs. Finally, our findings further verified that DAPT promotes the effects of CYP2J2 on cell viability, migration, and Notch signaling in hypoxia-induced HRVECs, while EDTA reversed the inhibitory effects of CYP2J2 on hypoxia-induced HRVECs. In conclusions, CYP2J2 was found to inhibit the viability and angiogenesis of HRVECs by inhibiting Notch signaling in a hypoxia-induced retinopathy model.

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“…Whilst pregnancies were unaffected in Jagged1 knockout mutant mice, Dll4 expression increased in capillary endothelial cells. Concomitant increase in Hey2 mRNA expression was observed, indicative of activated Notch signaling due to the loss of Jagged1 inhibition [134].…”

Section: Non-canonical Cell-autonomous Pathwaysmentioning

confidence: 99%

To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis

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Cruickshank

et al. 2021

Biomolecules

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Notch signaling forms an evolutionarily conserved juxtacrine pathway crucial for cellular development. Initially identified in Drosophila wing morphogenesis, Notch signaling has since been demonstrated to play pivotal roles in governing mammalian cellular development in a large variety of cell types. Indeed, abolishing Notch constituents in mouse models result in embryonic lethality, demonstrating that Notch signaling is critical for development and differentiation. In this review, we focus on the crucial role of Notch signaling in governing embryogenesis and differentiation of multiple progenitor cell types. Using hematopoiesis as a diverse cellular model, we highlight the role of Notch in regulating the cell fate of common lymphoid progenitors. Additionally, the influence of Notch through microenvironment interplay with lymphoid cells and how dysregulation influences disease processes is explored. Furthermore, bi-directional and lateral Notch signaling between ligand expressing source cells and target cells are investigated, indicating potentially novel therapeutic options for treatment of Notch-mediated diseases. Finally, we discuss the role of cis‑inhibition in regulating Notch signaling in mammalian development.

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Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy

Cited by 11 publications

References 59 publications

Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2

Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2

Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model

To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis

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