Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis

Takahashi, Nozomi; Harada, Miyuki; Hirota, Yasushi; Nose, Emi; Azhary, Jerilee Mariam Khong; Koike, Hiroshi; Kunitomi, Chisato; Yokosuka, Osamu; Izumi, Gentaro; Hirata, Tetsuya; Koga, Kaori; Wada‐Hiraike, Osamu; Chang, R. Jeffrey; Shimasaki, Shunichi; Fujii, Tomoyuki; Osuga, Yutaka

doi:10.1038/s41598-017-11252-7

Cited by 88 publications

(76 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…knowledge, to date, the regulation of TGF-β1 expression in granulosa cells is largely unknown. It has been shown that endoplasmic reticulum (ER) stress induces TGF-β1 expression in hGL cells 48 . Interestingly, ER stress stimulates VEGF expression in hGL cells, and inhibition of ER stress decreases VEGF expression in a rat OHSS model 49 .…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome

Fang

Wang

et al. 2020

Exp Mol Med

View full text Add to dashboard Cite

Ovarian hyperstimulation syndrome (OHSS) is one of the most serious and iatrogenic complications that can occur during in vitro fertilization treatment. Although the pathogenesis of OHSS is not fully understood, vascular endothelial growth factor (VEGF) has been recognized as an important mediator of the development of OHSS. Transforming growth factor-beta-1 (TGF-β1) is known to regulate various ovarian functions. However, whether VEGF can be regulated by TGF-β1 in human granulosa cells has not been determined. In addition, the role of TGF-β1 in the pathogenesis of OHSS remains unknown. In the present study, we demonstrate that TGF-β1 stimulates VEGF expression in and secretion from both immortalized human granulosa-lutein (hGL) cells and primary hGL cells. Our results demonstrate that the SMAD2/3, ERK1/2, and p38 MAPK signaling pathways are involved in TGF-β1-induced VEGF expression and secretion. Using a mouse OHSS model, we show that the expression levels of TGF-β1 and VEGF are increased in the ovaries of OHSS mice. Blocking TGF-β1 signaling inhibits the development of OHSS by attenuating VEGF expression. Moreover, clinical results reveal that the protein levels of TGF-β1 and VEGF are increased in the follicular fluid of patients with OHSS, and that the levels of these two proteins in the follicular fluid are positively correlated. The results of this study help to elucidate the mechanisms by which VEGF expression is regulated in hGL cells, which could lead to the development of alternative therapeutic approaches for treating OHSS.

show abstract

Section: Discussionmentioning

confidence: 99%

TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome

Fang

Wang

et al. 2020

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…In recent studies, it has been envisaged that the stroma of the ovaries with PCOS is expected to be stiffened due to the increase of teca cells and the thickened fibrotic albuginea. In animal experiments, the presence of fibrosis in ovarian tissue was histopathologically revealed [37][38][39][40][41]. In humans, fibrosis in the ovarian tissue can be demonstrated non-invasively with elastography [10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Is shear wave elastography relevant in the diagnosis of polycystic ovarian syndrome?

2019

View full text Add to dashboard Cite

Aim: The aim of this study was to determine the contribution of Shear Wave Elastography (SWE) to the diagnosis of polycystic ovarian syndrome (PCOS).Material and methods: Thirty-seven patients with PCOS diagnosis criteria were included in the study. Sixteen volunteer patients without hormonal disturbances and with normal menstrual cycles were evaluated as the control group. Gray scale ultrasonography (US) and SWE measurements in both ovaries were performed by a single radiologist who was blinded to the clinical and laboratory results.Results: The SWE measurements in PCOS group were 8.4±2.0 kPafor the right ovary and 9.4±3.9 kPa for the left ovary and in the control group 7.8±4.1 for the right ovary and 8.6±2.5 kPa for the left ovary. There was no statistically significant difference between the PCOS and the control group according to the SWE results (for right ovary p=0.356, for left ovary p=0.258, and total ovary p=0.293).Conclusions: The ovarian morphology isstill the most reliable imaging finding in the diagnosis of PCOS, although it is controversial especially among adolescents. Although the diagnostic efficacy of SWE is demonstrated in a variety of soft tissue lesions, we did not find any significant contribution of SWE to the diagnosis PCOS. Therefore, the promising value of elastography is yet to be defined for the diagnosis of PCOS.

show abstract

“…The beneficial effect of BGP-15 has been investigated in PCOS, as an ER stress inhibitor [48], in oxaliplatin therapy induced skeletal myopathy and ROS production [49], and in oxaliplatin induced intestinal dysfunction [50]. The investigations were carried out on BALB/c mice.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Reduction of interstitial fibrosis and collagen deposition in the ovaries [48] 3 mg/100g of body weight (BGP-15)…”

Section: Main Effect Dosementioning

confidence: 99%

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

et al. 2020

View full text Add to dashboard Cite

BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, diastolic dysfunction, tachycardia, heart failure, and atrial fibrillation, and it can alleviate cardiotoxicity. BGP-15 exhibits chemoprotective properties in different cytostatic therapies, and has also proven to be photoprotective. It can additionally have advantageous effects in mitochondrial-stress-related diseases. Although the precise mechanism of the effect is still unknown to us, we know that the molecule is a PARP inhibitor, chaperone co-inducer, reduces ROS production, and is able to remodel the organization of cholesterol-rich membrane domains. In the following review, our aim was to summarize the investigated molecular mechanisms and pharmacological effects of this potential API. The main objective was to present the wide pharmacological potentials of this chemical agent.

show abstract

Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis

Cited by 88 publications

References 58 publications

TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome

TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome

Is shear wave elastography relevant in the diagnosis of polycystic ovarian syndrome?

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

Contact Info

Product

Resources

About