Crucial role of hypoxia inducible factor in embryo implantation

2015 ◽  
Vol 112 ◽  
pp. 124
Author(s):  
Leona Matsumoto ◽  
Yasushi Hirota ◽  
Tomoko Saito-Fujita ◽  
Hirofumi Haraguchi ◽  
Mahiro Egashira ◽  
...  
2017 ◽  
Vol 29 (8) ◽  
pp. 1530 ◽  
Author(s):  
Jinhai Gou ◽  
Jia Jia ◽  
Juntao Feng ◽  
Xia Zhao ◽  
Tao Yi ◽  
...  

The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.


2013 ◽  
Vol 81 (7) ◽  
pp. 2562-2573 ◽  
Author(s):  
Christiane Beerlage ◽  
Jessica Greb ◽  
Dorothee Kretschmer ◽  
Mohammad Assaggaf ◽  
Philip C. Trackman ◽  
...  

ABSTRACTHypoxia-inducible factor 1 (HIF-1) is the key transcription factor involved in the adaptation of mammals to hypoxia and plays a crucial role in cancer angiogenesis. Recent evidence suggests a leading role for HIF-1 in various inflammatory and infectious diseases. Here we describe the role of HIF-1 inStaphylococcus aureusinfections by investigating the HIF-1-dependent host cell response. For this purpose, transcriptional profiling of HIF-1α-deficient HepG2 and control cells, both infected withStaphylococcus aureus, was performed. Four hours after infection, the expression of 190 genes, 24 of which were regulated via HIF-1, was influenced.LOX(encoding lysyl oxidase) was one of the upregulated genes with a potential impact on the course ofS. aureusinfection. LOX is an amine oxidase required for biosynthetic cross-linking of extracellular matrix components. LOX was upregulatedin vitroin different cell cultures infected withS. aureusand alsoin vivo, in kidney abscesses of mice intravenously infected withS. aureusand in clinical skin samples from patients withS. aureusinfections. Inhibition of LOX by β-aminopropionitrile (BAPN) did not affect the bacterial load in kidneys or blood but significantly influenced abscess morphology and collagenization. Our data provide evidence for a crucial role of HIF-1-regulated LOX in abscess formation.


2010 ◽  
Vol 206 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Daisuke Fujita ◽  
Akiko Tanabe ◽  
Tatsuharu Sekijima ◽  
Hekiko Soen ◽  
Keijirou Narahara ◽  
...  

During human pregnancy, trophoblasts play an important role in embryo implantation and placental development. Cytotrophoblast cells invade the uterine spiral arteries and differentiate into extravillous trophoblasts, resulting in the remodeling of the uterine vessels and fetoplacental vasculature. During early pregnancy, a physiologically hypoxic environment induces the production of angiogenic factors, such as vascular endothelial growth factor (VEGF), which are suggested to locally control the vascular remodeling. Endoglin, a cell-surface coreceptor for transforming growth factor-β1, is highly expressed in endothelial cells and syncytiotrophoblasts, and can be associated with endothelial nitric oxide synthase and vascular homeostasis. Several studies have recently suggested that some pregnancy-related complications, such as preeclampsia, have their origins early in pregnancy as a result of abnormalities in implantation and placental development. Although angiogenic factors are recognized as key molecules in placental development, little is known about the mechanism(s) of their regulation in trophoblasts. In this study, we elucidated the mechanisms underlying the regulation of VEGF and endoglin production under hypoxic conditions in the trophoblast-derived cell line, BeWo. We evaluated the role of the AKT–MTOR cascade and ERK kinase in the expression of VEGF and endoglin in response to hypoxia using various kinase inhibitors and small interfering RNA targeted against hypoxia-inducible factor (HIF)-1α (listed as HIF1A in Hugo Database). Our results suggest that both the phosphatidylinositol 3-kinase–AKT–MTOR–HIF-1α and ERK–HIF-1α signaling pathways are crucial for increasing VEGF and endoglin expression in response to hypoxia in BeWo cells.


Author(s):  
Adam Albanese ◽  
Leonard A. Daly ◽  
Daniela Mennerich ◽  
Thomas Kietzmann ◽  
Violaine Sée

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-&alpha; subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution and their effects on HIF-dependent signalling are discussed in this review.


2020 ◽  
Vol 22 (1) ◽  
pp. 268
Author(s):  
Adam Albanese ◽  
Leonard A. Daly ◽  
Daniela Mennerich ◽  
Thomas Kietzmann ◽  
Violaine Sée

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution, and their effects on HIF-dependent signalling are discussed in this review.


2001 ◽  
Vol 11 (PR11) ◽  
pp. Pr11-47-Pr11-52
Author(s):  
V. M. Pan ◽  
V. S. Flis ◽  
V. A. Komashko ◽  
O. G. Plys ◽  
C. G. Tretiatchenko ◽  
...  

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