Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1  and inhibits stromal cell-derived factor-1 in human endometrial stromal cells

Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu

doi:10.1093/humrep/der405

Cited by 55 publications

(56 citation statements)

References 37 publications

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“…Hypoxia attenuates the expression and production of SDF‐1 in ESC in a time‐dependent manner . Similar changes have been observed in ESC following stimulation with the hypoxia‐mimicking agent CoCl 2 in a dose‐dependent manner.…”

Section: Sdf‐1supporting

confidence: 70%

“…Hypoxia‐inducible factor‐1α has also been shown to bind directly to the hypoxia‐response elements (HRE) in the promoters of the genes encoding VEGF. We confirmed that hypoxia‐induced VEGF secretion was significantly attenuated by echinomycin . Echinomycin is a sequence‐specific DNA‐binding agent that binds to the HRE site within the promoters of the HIF‐1α target genes and selectively inhibits HIF‐1α binding activity .…”

Section: Vegfsupporting

confidence: 65%

“…Hypoxia has been shown to induce VEGF mRNA expression via activation of the hypoxia‐inducible factor‐1α (HIF‐1α) in human ESC . In addition, increased VEGF production was observed in ESC using CoCl 2 stimulation, a chemical hypoxia‐mimicking agent, which induces a hypoxia‐like condition by preventing the proteasomal degradation of HIF‐1α proteins.…”

Section: Vegfmentioning

confidence: 99%

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Regulation of decidualization and angiogenesis in the human endometrium: Mini review

Okada

Tsuzuki

Shindoh

et al. 2014

J of Obstet and Gynaecol

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Aim: The human endometrium is a dynamic tissue that undergoes regular cycles of menstruation, menstrual repair, proliferation and secretory differentiation in response to hypoxia and the female sex hormones. Methods: We identified new target genes that are regulated by progesterone during the decidualization of human endometrial stromal cells (ESC), including interleukin-15 (IL-15), fibulin-1 (FBLN-1), and heart and neural crest derivatives expressed transcript 2 (HAND2). Results: IL-15 is deeply involved in the hormonal control of the human endometrium by progesterone and may be important in embryo implantation. FBLN-1 has been shown to be an important extracellular matrix that mediates progesterone action in human ESC differentiation toward implantation. Moreover, progestininduced HAND2 is a transcription factor that contributes to the increased levels of FBLN-1 in human ESC. Several mediators, including vascular endothelial growth factor (VEGF), angiopoietin (ANGPT) and stromal cell-derived factor 1 (SDF-1), regulate human endometrial angiogenesis. Hypoxia increased the expression of VEGF and decreased the expression of SDF-1 in ESCs. Furthermore, hypoxia reduced ANGPT1 levels in ESC; however, ANGPT2 levels were unaffected. Estradiol simultaneously induced the expressions of VEGF and SDF-1, suppressing ANGPT1 production. Therefore, hypoxia and estradiol caused an increase in the ANGPT2/ANGPT1 ratio. Conclusion: Hypoxia and female sex hormones are involved in the regulation of angiogenic factors in an independent manner in human ESC. Analysis of the process of decidualization and angiogenesis in the human endometrium would provide useful information for the fields of reproductive biology, regenerative medicine and tissue engineering.

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Section: Sdf‐1supporting

confidence: 70%

Section: Vegfsupporting

confidence: 65%

Section: Vegfmentioning

confidence: 99%

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Regulation of decidualization and angiogenesis in the human endometrium: Mini review

Okada

Tsuzuki

Shindoh

et al. 2014

J of Obstet and Gynaecol

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“…These results suggested that resveratrol is involved in a different signaling pathway from HIF‐1α. In addition, increased VEGF production has been observed in ESCs after stimulation with CoCl 2 , a chemical that induces a hypoxia‐like condition by preventing proteasomal degradation of HIF‐1α proteins …”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia

Nishigaki

Kido

Kida

et al. 2020

Reprod Medicine & Biology

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Purpose Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (HIF)‐1α, and mitochondrial quantity in a steroidogenic human ovarian granulosa‐like tumor cell line (KGN) cells. Methods KGN cells were cultured with cobalt chloride (CoCl2; a hypoxia‐mimicking agent) and/or resveratrol. The mRNA and protein levels, protein secretion, and intracellular localization were assessed by real‐time PCR, Western blot analysis, ELISA, and immunofluorescence staining, respectively. Mitochondrial quantity was measured based on the mitochondrial DNA (mtDNA) copy number. Results CoCl2 simultaneously attenuated the levels of SIRT1 and mtDNA expression, and induced the levels of VEGF protein production. In contrast, resveratrol significantly increased the levels of SIRT1 and mtDNA copy number, but reduced VEGF production in normoxia. Resveratrol could recover CoCl2‐suppressed SIRT1 and mtDNA expression and antagonize CoCl2‐induced VEGF production. CoCl2 treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl2‐induced HIF‐1α and VEGF proteins. Conclusion These results suggest that resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway and inhibits VEGF induction through HIF‐1α under hypoxic conditions.

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“…The VEGF is a key mediator of physiological and pathological vascular remodeling . It can stimulate the proliferation and migration of endothelial cells, as well as vascular permeability .…”

Section: Functions Of Decidualizationmentioning

confidence: 99%

Decidualization of the human endometrium

Okada

Tsuzuki

Murata

2018

Reprod Medicine & Biology

252

176

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BackgroundDecidualization of the human endometrium, which involves a dramatic morphological and functional differentiation of human endometrial stromal cells (ESCs), is essential for the establishment of a successful pregnancy. Decidualization results from a complex interplay of transcription factors, morphogens, cytokines, cell cycle regulators, and signaling pathways.MethodsBased on a literature review, the regulation of, and the molecular mechanisms involved in, the decidualization of the endometrium are described.Main findingsProgesterone, together with proteins that are regulated by progesterone and/or cyclic adenosine monophosphate, including homeobox A10, forkhead box O1, signal transducers and activators of transcription, and heart and neural crest derivatives expressed transcript 2, forms a critical network for ESC decidualization and is a prerequisite to successful implantation. Decidualized ESCs contribute to the microenvironment at the feto–maternal interface and its direct or indirect influence on extracellular matrix remodeling, regulation of the local immune response, anti‐oxidative stress, and angiogenesis (vascular maturation). Impairment of this process is associated with a variety of pregnancy disorders, including infertility, recurrent miscarriages, and uteroplacental disorders.ConclusionA deeper understanding of the process of decidualization is expected to provide new insights into the fields of reproductive biology and reproductive medicine.

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Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1 and inhibits stromal cell-derived factor-1 in human endometrial stromal cells

Abstract: Hypoxia simultaneously acts to increase VEGF via HIF-1α and to decrease SDF-1 in a HIF-1α-independent manner in ESCs. These results indicate a potential mechanism for the action of hypoxic conditions that could influence angiogenesis in the human endometrium.

Cited by 55 publications

References 37 publications

Regulation of decidualization and angiogenesis in the human endometrium: Mini review

Regulation of decidualization and angiogenesis in the human endometrium: Mini review

Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia

Decidualization of the human endometrium

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