Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage

Huang, Jianfang; Mao, Yuling; Li, Quanxin; Hong, Honghai; Tang, Ni; Kang, Xiangjin; Huang, Yu‐Ling; Liu, Jianqiao; Gong, Qiyong; Yao, Yachao; Li, Lei

doi:10.1111/jcmm.17491

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…Angiogenesis-related proteins are closely associated with the pathophysiology of OHSS 36 , 37 . EGR1 is a key regulator of angiogenesis 38 .…”

Section: Discussionmentioning

confidence: 99%

EGR1 Promotes Ovarian Hyperstimulation Syndrome Through Upregulation of SOX9 Expression

Wang,

Chen,

Huang

et al. 2023

Cell Transplant

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Angiogenesis is strongly associated with ovarian hyperstimulation syndrome (OHSS) progression. Early growth response protein 1 (EGR1) plays an important role in angiogenesis. This study aimed to investigate the function and mechanism of EGR1 involved in OHSS progression. RNA-sequencing was used to identify differentially expressed genes. In vitro OHSS cell model was induced by treating KGN cells with human chorionic gonadotropin (hCG). In vivo OHSS model was established in mice. The expression levels of EGR1, SOX1, and VEGF were determined by Quantitative Real-Time polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence staining, and immunochemistry assay. The content of VEGF in the culture medium of human granulosa-like tumor cell line (KGN) cells was accessed by the ELISA assay. The regulatory effect of EGR1 on SRY-box transcription factor 9 (SOX9) was addressed by luciferase reporter assay and chromatin immunoprecipitation. The ERG1 and SOX9 levels were significantly upregulated in granulosa cells from OHSS patients and there was a positive association between EGR1 and SOX9 expression. In the ovarian tissues of OHSS mice, the levels of EGR1 and SOX9 were also remarkedly increased. Treatment with hCG elevated the levels of vascular endothelial growth factor (VEGF), EGR1, and SOX9 in KGN cells. Silencing of EGR1 reversed the promoting effect of hCG on VEGF and SOX9 expression in KGN cells. EGR1 transcriptionally regulated SOX9 expression through binding to its promoter. In addition, administration of dopamine decreased hCG-induced VEGF in KGN cells and ameliorated the progression of OHSS in mice, which were companied with decreased EGR1 and SOX9 expression. EGR1 has a promoting effect on OHSS progression and dopamine protects against OHSS through suppression of EGR1/SOX9 cascade. Our findings may provide new targets for the treatment of OHSS.

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“…Angiogenesis-related proteins are closely associated with the pathophysiology of OHSS 36 , 37 . EGR1 is a key regulator of angiogenesis 38 .…”

Section: Discussionmentioning

confidence: 99%

EGR1 Promotes Ovarian Hyperstimulation Syndrome Through Upregulation of SOX9 Expression

Wang,

Chen,

Huang

et al. 2023

Cell Transplant

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“…Permeability assay was performed as previously described (Huang et al 2022 ). Briefly, mice were injected with 0.1 mL Evans blue (5 mM; MilliporeSigma, Merck, Darmstadt, Germany) through the caudal vein after anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, several cytokines and angiogenic molecules, including vascular endothelial growth factor (VEGF), have been involved in the pathogenesis of OHSS (Wang et al 2021 ). Previous studies indicated that the effective inhibition of the VEGF-related vascular permeability via targeting VEGF secretion could prevent the progression of OHSS (Hortu et al 2021 ; Huang et al 2022 ; Zhang et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D3 reduces the symptoms of ovarian hyperstimulation syndrome in mice and inhibits the release of granulosa cell angiogenic factor through pentraxin 3

Zhang,

Chen,

et al. 2024

In Vitro Cell.Dev.Biol.-Animal

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It has been reported that the effective inhibition of vascular endothelial growth factor (VEGF) can prevent the progression of ovarian hyperstimulation syndrome (OHSS). The present study aimed to investigate the mechanism underlying the effect of vitamin D3 (VD3) on OHSS in mouse models and granulosa cells. The effects of VD3 administration (16 and 24 IU) on ovarian permeability were determined using Evans blue. In addition, ovarian pathology, corpus luteum count, inflammatory responses, and hormone and VEGFA levels were assessed using pathological sections and ELISA. Molecular docking predicted that pentraxin 3 (PTX3) could be a potential target of VD3, and therefore, the effects of human chorionic gonadotropin (hCG) and VD3 as well as PTX3 overexpression on the production and secretion of VEGFA in granulosa cells were also investigated using western blotting and immunofluorescence. Twenty-four IU VD3 significantly reversed the increase in ovarian weight and permeability in mice with OHSS. Additionally, VD3 diminished congestion and the number of corpus luteum in the ovaries and reduced the secretion levels of inflammatory factors and those of estrogen and progesterone. Notably, VD3 downregulated VEGFA and CD31 in ovarian tissues, while the expression levels of PTX3 varied among different groups. Furthermore, VD3 restored the hCG-induced enhanced VEGFA and PTX3 expression levels in granulosa cells, whereas PTX3 overexpression abrogated the VD3-mediated inhibition of VEGFA production and secretion. The present study demonstrated that VD3 could inhibit the release of VEGFA through PTX3, thus supporting the beneficial effects of VD3 administration on ameliorating OHSS symptoms.

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Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage

Huang

Mao

et al. 2022

J Cellular Molecular Medi

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Angiogenesis and increased permeability are essential pathological basis for the development of ovarian hyperstimulation syndrome (OHSS). Kallistatin (KS) is an endogenous anti‐inflammatory and anti‐angiogenic factor that participates in a variety of diseases, but its role in OHSS remains unknown. In this study, treating a human ovarian granulosa‐like tumour cell line KGN and human primary granulosa cells (PGCs) with human chorionic gonadotropin (hCG) reduced the expression of KS, but increased the expression of VEGF. Furthermore, we found that KS could attenuate the protein level of VEGF in both KGN cells and human PGCs. More interestingly, we observed that exogenous supplementation of KS significantly inhibited a series of signs of OHSS in mice, including weight gain, ovarian enlargement, increased vascular permeability and up‐regulation of VEGF expression. In addition, KS was proved to be safe on mice ovulation, progression of normal pregnancy and fetus development. Collectively, these findings demonstrated that KS treatment prevented OHSS, at least partially, through down‐regulating VEGF expression. For the first time, these results highlight the potential preventive value of KS in OHSS.

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Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage

Cited by 4 publications

References 46 publications

EGR1 Promotes Ovarian Hyperstimulation Syndrome Through Upregulation of SOX9 Expression

EGR1 Promotes Ovarian Hyperstimulation Syndrome Through Upregulation of SOX9 Expression

Vitamin D3 reduces the symptoms of ovarian hyperstimulation syndrome in mice and inhibits the release of granulosa cell angiogenic factor through pentraxin 3

Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage

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