Leukemia inhibitory factor prevents chicken follicular atresia through PI3K/AKT and Stat3 signaling pathways

Dong, Jun; Guo, Changquan; Zhou, Shaojun; An, Zhen; Li, Jian; Mi, Yuling; Zhang, Caiqiao

doi:10.1016/j.mce.2021.111550

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…Subsequently, SS-treated KGN cells silencing Stat3 was combined with MT treatment, after which the KGN cell viability was reduced and cell autophagy was promoted. Previous study has proved that leukemia inhibitory factor exerts a repressing effect on GC autophagic cell death via stimulating PI3K/Akt and Stat3 pathways and further alleviates follicular atresia [ 51 ], further supporting that Stat3 knockdown can counteract the role of MT in SS-induced KGN cell autophagy.…”

Section: Discussionmentioning

confidence: 80%

Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

Zhao

et al. 2022

BMC Women's Health

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Objectives Premature ovarian insufficiency (POI) refers to the decline and cessation of ovarian functions in women under 40 years of age. Melatonin (MT) acts as a protective for the ovary. This study elucidated the role of MT in autophagy of granulosa cells (GCs) in POI via modulating the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway. Methods The expression levels of microRNA (miR)-15a-5p, signal transducer and activator of transcription 3 (Stat3), and relevant hormones in the clinically collected serum samples of POI patients and healthy controls were examined. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received MT treatment. The expression levels of miR-15a-5p, Stat3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in KGN cells were tested via quantitative real-time polymerase chain reaction and Western blotting. KGN cell viability was assessed by MTT assay and the protein levels of autophagy-related markers Beclin-1, microtubule-associated protein light chain 3 II/I, and p62 were detected by Western blotting. The binding relation between miR-15a-5p and Stat3 was verified via the dual-luciferase reporter gene assay. Functional rescue experiments were performed to probe the underlying role of miR-15a-5p/Stat3/the PI3K-Akt-mTOR pathway in KGN cell autophagy. Results miR-15a-5p was increased whilst Stat3 was decreased in the serum of POI patients and SS-induced KGN cells. MT inhibited miR-15a-5p and Stat3, activated the PI3K-Akt-mTOR pathway, and repressed cell autophagy in SS-induced KGN cells. miR-15a-5p targeted and repressed Stat3 expression. Upregulation of miR-15a-5p or downregulation of Stat3 or the PI3K-Akt-mTOR pathway promoted KGN cell autophagy. Conclusion MT suppressed miR-15a-5p and activated Stat3 and the PI3K-Akt-mTOR pathway, finally impeding SS-induced autophagy of GCs.

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Section: Discussionmentioning

confidence: 80%

Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

Zhao

et al. 2022

BMC Women's Health

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“…STAT1 and STAT3 are expressed in granulosa cells, specifically in the primordial follicles 24 . Emerging evidence has shown that STAT3 prevents follicular atresia and enhances ovarian function in POI animal models 25,26 . The mitogen‐activated protein kinase (MAPKs), members of the serine/threonine‐protein kinase family, are involved in cell proliferation, differentiation, growth, and many other physiological processes.…”

Section: Discussionmentioning

confidence: 99%

“…24 Emerging evidence has shown that STAT3 prevents follicular atresia and enhances ovarian function in POI animal models. 25,26 The mitogen-activated protein kinase (MAPKs), members of the serine/threonine-protein kinase family, are involved in cell proliferation, differentiation, growth, and many other physiological processes. MAPK1, also known as extracellular signal-regulated kinase 2 (ERK2), plays an essential role in regulating the gonadotropin LH-β and FSH-β expression, oocyte meiotic maturation, and ovulation.…”

Section: Targetmentioning

confidence: 99%

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

Kong,

Cho,

Hwang

et al. 2023

J of Cellular Biochemistry

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Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha‐lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA‐related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein–protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein‐to‐protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.

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“…In growing follicles, the fate of GCs (proliferation, differentiation, or apoptosis) is regulated by the complex coordination between gonadotropins and ovarian regulatory factors, such as GnRH, FSH, leukemia inhibitory factor (LIF), fibroblast growth factor (bFGF), PGE2, etc. [ 34 , 35 , 36 ]. Almost all gonadotropins can promote GC proliferation and inhibit follicular atresia, with FSH displaying the highest efficiency.…”

Section: Discussionmentioning

confidence: 99%

Follicle-Stimulating Hormone Alleviates Ovarian Aging by Modulating Mitophagy- and Glycophagy-Based Energy Metabolism in Hens

Dong

Guo

Yang

et al. 2022

Cells

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As a predominant hormone in the reproductive axis, follicle-stimulating hormone (FSH) is known as the primary surviving factor for follicular growth. In this study, the alleviating effect of FSH on aging chicken granulosa cells (GCs) was investigated. Results showed that FSH activated mitophagy and relieved mitochondrial edema in D-gal-induced senescent GCs, which was evidenced by an increased number of mitophagosomes as well as increased mitochondria-light chain 3 (LC3) colocalization. Mitophagy activation was accompanied by the activation of the AMP-activated protein kinase (AMPK) signaling pathway. Furthermore, upregulated glycophagy was demonstrated by an increased interaction of starch-binding domain protein 1 (STBD1) with GABA type A receptor-associated protein-like 1 (GABARAPL1) in D-gal-induced senescent GCs. FSH treatment further promoted glycophagy, accompanied by PI3K/AKT activation. PI3K inhibitor LY294002 and AKT inhibitor GSK690693 attenuated the effect of FSH on glycophagy and glycolysis. The inhibition of FSH-mediated autophagy attenuated the protective effect of FSH on naturally aging GC proliferation and glycolysis. The simultaneous blockage of PI3K/AKT and AMPK signaling also abolished the positive effect of FSH on naturally senescent ovarian energy regulation. These data reveal that FSH prevents chicken ovarian aging by modulating glycophagy- and mitophagy-based energy metabolism through the PI3K/AKT and AMPK pathways.

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Leukemia inhibitory factor prevents chicken follicular atresia through PI3K/AKT and Stat3 signaling pathways

Cited by 8 publications

References 36 publications

Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

Follicle-Stimulating Hormone Alleviates Ovarian Aging by Modulating Mitophagy- and Glycophagy-Based Energy Metabolism in Hens

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