Leukemia inhibitory factor induces corticotropin-releasing hormone in mouse trophoblast stem cells

Wang, He; Tsukada, Tsuyoshi; Shimada, Hiroki; Sakata‐Haga, Hiromi; Iida, Yasuo; Zhang, Shitai; Shoji, Hiromichi; Hatta, Toshihisa

doi:10.1016/j.bbrc.2019.11.059

Cited by 4 publications

(6 citation statements)

References 27 publications

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“…In human placenta, CRH biosynthesis and secretion from trophoblasts gradually increase until the end of pregnancy ( Smith et al, 2012 ). Previous studies have shown that only anthropoid primate species express placental CRH ( Bowman et al, 2001 ); however, because of advancements in instrumentation, several researchers have since quantified murine placental Crh mRNA and protein ( Wang et al, 2016 , 2020 ; Zhou et al, 2016 ). Consistent with these findings, we also found CRH in mouse placenta.…”

Section: Discussionmentioning

confidence: 99%

“…LIF is the most pleiotropic member of the IL-6 family of cytokines. After binding to its receptor gp130 (also known as Il6st), LIF initiates a cascade of tyrosine phosphorylation that stimulates three distinct signaling pathways, the JAK/STAT3, MAPK, and PI3K/AKT pathways ( Fahmi et al, 2013 ), among which the MAPK and PI3K/AKT pathways are involved in LIF-induced upregulation of CRH in mTSCs ( Wang et al, 2020 ). JAK/STAT3 is the most commonly stimulated pathway by LIF; this pathway is involved in LIF-induced Pomc expression and ACTH secretion in murine trophoblasts and cells from a corticotroph cell line ( Simamura et al, 2010 ; Tsukada et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Protocols for mTSC maintenance and differentiation were based on previously published methods ( Erlebacher et al, 2004 ; Natale et al, 2009 ; Wang et al, 2020 ). For differentiation on culture day 8, cells were treated with recombinant mouse LIF (Millipore, Darmstadt, Germany) after which the medium was changed daily.…”

Section: Methodsmentioning

confidence: 99%

“…However, the underlying mechanism by which maternal LIF induces placental ACTH secretion remains unclear. Recently, we found that LIF induces corticotropin-releasing hormone (CRH) in differentiated mouse trophoblast stem cells (mTSCs) ( Wang et al, 2020 ). CRH is a peptide hormone in the hypothalamus, and its main function is stimulation of ACTH synthesis in the pituitary as part of the hypothalamic-pituitary-adrenal axis.…”

Section: Introductionmentioning

confidence: 99%

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Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast

Wang

Sakata‐Haga

Masuta

et al. 2021

Front. Cell Dev. Biol.

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We previously showed that maternal leukemia inhibitory factor (LIF) induces placental production of adrenocorticotropic hormone (ACTH), which stimulates fetal nucleated red blood cells to further secrete LIF and promote neurogenesis in rodent brains. However, the underlying mechanism of LIF-dependent ACTH induction remains unclear. Recently, we found that LIF induces corticotropin-releasing hormone (CRH) in mouse trophoblast stem cells. This finding supports the results of a previous study that CRH, which is produced by the placenta, induces placental ACTH production. In this study, we examined whether the effects of LIF are mediated by the induction of Pomc via CRH upregulation in mouse trophoblast. In vivo, protein levels of LIF and CRH peak in mouse placenta at 13.5 days post coitum. In mouse placenta, Crh mRNA and protein levels significantly increased 3 h after intraperitoneal injection of LIF (5 μg/kg body weight) into dams at 13.5 days post coitum. We also examined the effect of LIF-induced CRH on the expression of Pomc induced by LIF in mouse trophoblast stem cells in vitro. After LIF supplementation for 3 days, we found that the increased expression of Crh-induced by new supplementation of LIF was earlier than that of Pomc. Furthermore, LIF-induced upregulation of Pomc in mouse trophoblast stem cells was attenuated by inhibition of the CRH/CRHR1 pathway, whereas LIF-induced secretion of ACTH was attenuated by inhibition of the JAK/STAT3 pathway. Therefore, LIF indirectly increases placental Pomc expression through the CRH/CRHR1 pathway, and placental ACTH secretion is induced directly by LIF via the JAK/STAT3 pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast

Wang

Sakata‐Haga

Masuta

et al. 2021

Front. Cell Dev. Biol.

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“…We have previously reported that LIF levels in cerebrospinal fluid (CSF) exhibited a peak at E13 to E14 in mice [ 13 ] and at E15.5 in rats [ 14 ]. Interestingly, maternal LIF does not pass through the placenta but induces placental trophoblasts to produce the adrenocorticotropic hormone, which then promotes the secretion of LIF from fetal nucleated red blood cells, thus leading to a surge of LIF in the fetal CSF [ 14 , 15 , 16 , 17 , 18 ]. Finally, an increased level of LIF in fetal CSF enhanced NPC proliferation in the subventricular zone/ventricular zone (SVZ/VZ) at E15.5 in rats [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

LIF–IGF Axis Contributes to the Proliferation of Neural Progenitor Cells in Developing Rat Cerebrum

Takata

Sakata‐Haga

Shimada

et al. 2022

IJMS

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In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF–IGF axis in cerebral cortical development in an autocrine/paracrine manner.

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

Dong

Guo

Zhou

et al. 2022

Molecular and Cellular Endocrinology

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Leukemia inhibitory factor induces corticotropin-releasing hormone in mouse trophoblast stem cells

Cited by 4 publications

References 27 publications

Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast

Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast

LIF–IGF Axis Contributes to the Proliferation of Neural Progenitor Cells in Developing Rat Cerebrum

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

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