Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts

Kojima, Kenji; Kanzaki, Hideharu; Iwai, Mieko; Hatayama, Hiroshi; Fujimoto, Mai; Narukawa, Shinji; Higuchi, Toshihiro; Kaneko, Yoshiyuki; Mori, Takahide; Fujita, Jun

doi:10.1093/molehr/1.5.249

Cited by 29 publications

(28 citation statements)

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“…Earlier reports also suggested that the high levels of plasma ACTH raised the levels of leukemia inhibitory factor (LIF) in the fetal cerebrospinal fluid (CSF). It is well established that LIF has an important role during embryonic cerebral differentiation [8][9][10]. In the present study, the maximal level of ACTH was secreted at gd 6 in the control C57BL/6j mice.…”

Section: Discussionsupporting

confidence: 58%

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The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

Hiramoto

Yamate²,

Sato³

2014

Biol Med (Aligarh)

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Gp91phox NADPH oxidase enzyme was established earlier to play its role in generating reactive oxygen species. In recent studies, gp91phox NADPH oxidase was reported to be involved in the regulation of ovulation and oestrial cycle. However, its mechanism of action during comparatively stressful gestational period 'gp' is not known. Current study was designed to investigate the role of gp91phox NADPH oxidase during 'gp' by using gp91phox deficient (gp91phox -/-) mice whereas C57BL/6j mice in graviditas served as control. During 'gp' period the floating time (akinesia time) in control group was found to be highest on day 6, which gradually decreased towards parturition. Conversely, ingp91phox -/-mice, there was no such recognizable alteration during 'gp' as compared to control C57BL/6j mice. In addition, plasma level of adrenocorticotropic hormone (ACTH) was significantly higher on day 6 (gp) in the control mice. Similarly, the level of growth hormone (GH) was also found elevated during 'gp' in control mice. On the other side, in thegp91phox -/-mice, no such increase in ACTH or GH levels as compared to C57BL/6j mice was observed. It is worth mentioning that GH levels (gp) ingp91phox -/-mice were found ever lower than those of the control C57BL/6j mice. There were also fewer newborngp91phox -/-mice compared with C57BL/6j mice; interestingly, the number of fetalgp91phox -/-mice did not decrease until after gd 6. Furthermore, the average weight for the newborngp91phox -/-mice was significantly lower than the C57BL/6j mice. The results of the present study deonstrated that gp91phox NADPH oxidase is required during relatively stressful gestational period 'gp' and may play a role during fetal differentiation and growth.

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Section: Discussionsupporting

confidence: 58%

“…Moreover, the number of fetal mice decreased between gd 6 and gd 10. For this reason, we speculate that LIF was not secreted, and due to a deficit of ACTH from the placenta, differentiation of the systemic nervosum did not progress [8][9][10].…”

Section: Discussionmentioning

confidence: 99%

The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

Hiramoto

Yamate²,

Sato³

2014

Biol Med (Aligarh)

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“…During pregnancy, LIF is synthesised by the decidua -the maternal part of the placenta -and by Th2 lymphocytes whereas the syncytiotrophoblast expresses LIF-R [13] ( Figure 2b). The exact function of the LIF/LIF-R molecules during pregnancy is still unknown but the binding of LIF on its receptor might favour trophoblastic growth and differentiation [14]. This mechanism is also closely related to other immune mechanisms implicated in the foetomaternal tolerance, such as the Th1/Th2 balance and regulation by progesterone.…”

Section: Leukemia Inhibitory Factor and Its Receptormentioning

confidence: 99%

Tolerance to the foeto-placental ‘graft’: ten ways to support a child for nine months

Thellin

Coumans

Zorzi

et al. 2000

Current Opinion in Immunology

196

109

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“…Although the LIFR is undetectable in nonpregnant endometrium, LIFR mRNA is highly expressed in the chorionic villus during the first trimester and in term placenta (24), suggesting that LIFR may play a regulatory role in trophoblast growth and differentiation in the human placenta. These observations indicate the important functions of LIF/LIFR system in placental development and pregnancy, and are supported by the LIF/LIFR knockout results.…”

mentioning

confidence: 99%

“…The minimal enhancer, 226 bp, increases heterologous promoter activity 10 -35-fold when placed upstream or downstream of the reporter gene in either orientation (25). Within this 226-bp region, several potential transcription factor binding sites were predicted, but site-directed mutagenesis failed to correlate two transcription factors, Sp1 and NF-B, with enhancer activity (24). Here we report a detailed characterization of this minimal enhancer with three critical elements contributing to the enhancer activity, an Oct-1 binding site at Ϫ4617/Ϫ4602 site; a GATA-like element at Ϫ4549/Ϫ4535 site, and a novel placenta-specific element (PSE) at Ϫ4464/Ϫ4445.…”

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confidence: 99%

Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene

Wang

Melmed

1998

Journal of Biological Chemistry

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We recently reported a placenta-specific enhancer in the human leukemia inhibitory factor receptor (LIFR) gene and now show detailed characterization of the 226-base pair enhancer (؊4625/؊4400 nucleotides). Four of twenty-two mutants in linker analysis showed reduced promoter activities to 45, 30, 10, and 10%, respectively. Specific binding of region A (؊4617/؊4602) with nuclear extract was competed by a known Oct-1 oligo and supershifted by Oct-1 antibody. Specific binding of region B (؊4549/؊4535) was competed by a GATA oligo, but could not be supershifted by four GATA antibodies. Nevertheless, mutagenesis showed that critical bases in region B were identical to the GATA core motif, indicating that region B may bind to a novel GATA family transcription factor. The other two adjacent regions designated as region C (؊4464/؊4445) showed no known consensus binding sites, and their specific placental JEG-3 nuclear extract binding was not evident in nonplacental nuclear extracts and was not competed by a trophoblast specific element (TSE), indicating that region C is a novel placenta-specific element (PSE, CATTTCCTGAACTAGTT-TTT). Footprinting localized the binding boundary of PSE-binding protein (PSEB), and three Gs were found to be important for specific PSE binding. UV cross-linking showed that PSEB had a molecular mass of ϳ160 kDa, substituting the PSE with two previously reported placenta elements TSE or chorionic somatomammotropin enhancer factor 1 (CSEF-1) motifs resulted in markedly different promoter activities, indicating that PSEB is indeed different from TSE binding protein or CSEF-1. These results are the first demonstration that a novel PSE is the major element for placenta-specific enhancer activity in human LIFR gene.

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Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts

Cited by 29 publications

References 0 publications

The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

Tolerance to the foeto-placental ‘graft’: ten ways to support a child for nine months

Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene

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