Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells

Han, Ying; Yao, Ruqiang; Yang, Zexin; Li, Shuang; Wei, Meng; Zhang, Yinfeng; Zhang, Yunshan; Luo, Haining

doi:10.1016/j.yexcr.2021.113002

Cited by 17 publications

(11 citation statements)

References 33 publications

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“…Besides LH and prolactin, insulin can also be considered an endocrine luteotropic factor in the canine CL (36) and its contribution to E2 production cannot be ruled out (25). The mechanism of E2 binding to ERa and leading to proliferation is opposed to binding to ERb (47) leading to expression of anti-proliferative genes such as p-53, PI3K and Akt, as well as the increase of stress associated and apoptosis related proteins (48), as also observed in our study.…”

Section: Discussionsupporting

confidence: 84%

An approach to uncover the relationship between 17b-estradiol and ESR1/ESR2 ratio in the regulation of canine corpus luteum

et al. 2022

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The canine corpus luteum (CL) is able to synthetise, activate and deactivate 17b-estradiol (E2) and also expresses nuclear estrogen receptors in a time-dependent manner during diestrus. Nevertheless, we are still missing a better comprehension of E2 functions in the canine CL, especially regarding the specific roles of estrogen receptor alpha (ERa) and ERb, encoded by ESR1 and 2, respectively. For that purpose, we analyzed transcriptomic data of canine non-pregnant CL collected on days 10, 20, 30, 40, 50 and 60 of diestrus and searched for differentially expressed genes (DEG) containing predicted transcription factor binding sites (TFBS) for ESR1 or ESR2. Based on biological functions of DEG presenting TFBS, expression of select transcripts and corresponding proteins was assessed. Additionally, luteal cells were collected across specific time points during diestrus and specificity of E2 responses was tested using ERa and/or ERb inhibitors. Bioinformatic analyses revealed 517 DEGs containing TFBS, from which 67 for both receptors. In general, abundance of predicted ESR1 targets was greater in the beginning, while abundance of ESR2 targets was greater in the end of diestrus. ESR1/ESR2 ratio shifted from an increasing to a decreasing pattern from day 30 to 40 post ovulation. Specific receptor inhibition suggested an ERa-mediated positive regulation of CL function at the beginning of diestrus and an ERb-mediated effect contributing to luteal regression. In conclusion, our data points toward a broad spectrum of action of E2 and its nuclear receptors, which can also act as transcription factors for other genes regulating canine CL function.

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Section: Discussionsupporting

confidence: 84%

An approach to uncover the relationship between 17b-estradiol and ESR1/ESR2 ratio in the regulation of canine corpus luteum

et al. 2022

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“…Chronic inflammation is a major factor involved in the pathogenesis of POI. Inflammation is related to folliculogenesis and its dysregulation contributes to impaired oocyte quality and POI disease [ 28 ]. Increased expression of inflammatory indices in patients with POI, such as the neutrophil to lymphocyte ratio (NLR), oxidative stress index and increased expression of proinflammatory cytokines and transcription factors (e.g NF-κB) indicate their involvement in POI pathogenesis [ 21 ].…”

Section: Poi Pathogenesis Featuresmentioning

confidence: 99%

Protective role of stem cells in POI: Current status and mechanism of action, a review article

Sadeghi,

Mosaffa,

Huang

et al. 2024

Heliyon

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“…Existing studies have implicated that OS is of great importance in the development and perpetuation of inflammation, increasing the levels of inflammatory factors such as tumor necrosis factor-a (TNF-a), IL-1b, IL-6, and TGF-b in vivo (164). Han et al (165) detected that elevated levels of IL-4, IL-1b, and IL-6 in follicular fluid samples and GCs from POI patients, and further found that IL-4 could activate the PI3K/AKT signaling pathway, promote apoptosis, and inhibit GCs proliferation in in vitro experiments. Besides, inflammatory factors can also activate NF-kB signaling pathway and affect the expression of follicle-stimulating hormone receptor(FSHR) through glucose-regulated protein 78-mediated ER stress to promote GCs proliferation.…”

Section: Low-level Chronic Inflammatory State In Poimentioning

confidence: 99%

Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants

Shi,

Zhu,

Zhang

et al. 2023

Front. Endocrinol.

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Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis in ovarian tissue. When the balance between ROS and antioxidants is disrupted, however, it can cause serious consequences of oxidative stress (OS), and the quantity and quality of oocytes will decline. Therefore, this review discusses the interrelationship between OS and premature ovarian insufficiency (POI), the potential mechanisms and the methods by which antioxidants can improve POI through controlling the level of OS. We found that OS can mediate changes in genetic materials, signal pathways, transcription factors and ovarian microenvironment, resulting in abnormal apoptosis of ovarian granulosa cells (GCs) and abnormal meiosis as well as decreased mitochondrial Deoxyribonucleic Acid(mtDNA) and other changes, thus accelerating the process of ovarian aging. However, antioxidants, mesenchymal stem cells (MSCs), biological enzymes and other antioxidants can delay the disease process of POI by reducing the ROS level in vivo.

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Interleukin-4 activates the PI3K/AKT signaling to promote apoptosis and inhibit the proliferation of granulosa cells

Cited by 17 publications

References 33 publications

An approach to uncover the relationship between 17b-estradiol and ESR1/ESR2 ratio in the regulation of canine corpus luteum

An approach to uncover the relationship between 17b-estradiol and ESR1/ESR2 ratio in the regulation of canine corpus luteum

Protective role of stem cells in POI: Current status and mechanism of action, a review article

Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants

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