scholarly journals IGFBP-1 forms associated with placental cell membranes

2009 ◽  
Vol 74 (7) ◽  
pp. 707-716 ◽  
Author(s):  
Romana Masnikosa ◽  
Bogovid Zivkovic ◽  
Olgica Nedic
Keyword(s):  
Molecular Mass ◽  
Cell Membranes ◽  
High Molecular Mass ◽  
Matrix Metalloproteases ◽  
Placental Development ◽  
Placental Cell ◽  
Igf Receptors ◽  
Igf Binding ◽  
And Function ◽  
Igf Binding Protein

Fetal growth in utero depends on the proper development and function of the placenta. Insulin-like growth factors (IGFs) are critically involved in placental development. During pregnancy, an IGF-binding protein, IGFBP-1, which is produced by maternal decidua, plays an important role in the control of the bioavailability of IGFs. It has recently been proposed that cleavage of decidual IGFBP-1 by matrix metalloproteases is a novel mechanism in the control of placental development. The presence of IGFBP-1 in solubilized placental cell membranes, i.e. its association with the membranes, was detected in an earlier work. Herein, it is shown that IGFBP-1 from the solubilized membranes forms dimers, as well as high molecular mass complexes. IGFBP-1 dimers preferably contain the non-phosphorylated form of IGFBP-1. The high molecular mass forms are polymers of IGFBP-1 or its complexes with other membrane proteins. Dimerization of IGFBP-1, together with its association with the placental cell membrane, could serve as an additional mechanism of the regulation of IGF availability to the type 1 IGF receptors.

Developmentally regulated expression of insulin-like growth factors by differentiated murine teratocarcinomas and extraembryonic mesoderm

Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 193-212
Author(s):  
John K. Heath ◽  
Wai-Kang Shi
Keyword(s):  
Plasma Membrane ◽  
Binding Protein ◽  
Membrane Receptors ◽  
Developmentally Regulated ◽  
Igf Receptors ◽  
Igf Binding ◽  
Plasma Membrane Receptors ◽  
Igf Binding Protein ◽  
Culture Supernatants ◽  
Insulin Like Growth Factors

The expression of plasma membrane receptors for insulin-like growth factors (IGFs) by PC13 embryonal carcinoma (EC) cells, and their immediate differentiated progeny PC13END was examined by binding radiolabelled IGF-I to cell monolayers. Both cell types express high-affinity IGF receptors, but the apparent number of unoccupied receptor sites falls by about 60% upon differentiation. Crosslinking studies reveal that both type 1 and type 2 IGF receptors are expressed by PC13EC cells. PC13END-cell-conditioned medium contains developmentally regulated, separable activities, one of which reacts directly with IGF-II, and the other with IGF for plasma membrane receptors. The former activity represents a soluble secreted IGF-binding protein. The latter activity is structurally and functionally similar to rat IGF-II. Polyclonal antibodies raised against purified rat IGF-II specifically recognize multiple forms of IGF in radiolabelled culture supernatants and material which closely resembles the soluble IGF-binding protein. Immunoprecipitation of radiolabelled culture supernatants with anti-rat IGF-II reveals that the differentiation of PC13EC cells is accompanied by the coexpression of IGF-like molecules and the soluble binding protein, and that IGF-like molecules are expressed by extraembryonic tissues of mesodermal origin in the early postimplantation mouse embryo. These findings show that IGF-like molecules are expressed in early mammalian development and may act in an autocrine fashion in vivo.

scholarly journals Myostatin regulates pituitary development and hepatic IGF1

2019 ◽  
Vol 316 (6) ◽  
pp. E1036-E1049 ◽  
Author(s):  
Wioletta Czaja ◽  
Yukiko K. Nakamura ◽  
Naisi Li ◽  
Jennifer A. Eldridge ◽  
David M. DeAvila ◽  
...  
Keyword(s):  
Striated Muscle ◽  
Muscle Growth ◽  
Unintended Consequences ◽  
Pituitary Development ◽  
Igf Binding ◽  
Acid Labile Subunit ◽  
Muscle Wasting Disease ◽  
And Function ◽  
Igf Binding Protein ◽  
Igf1 Expression

Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice. This correlated with increased levels of GH, prolactin, and the cells that secrete these hormones, somatotropes and lactotropes, respectively, in Jekyll pituitaries. Recombinant myostatin also stimulated GH release and gene expression in pituitary cell cultures although inhibiting prolactin release. In primary hepatocytes, recombinant myostatin blocked GH-stimulated expression of two key mediators of growth, insulin-like growth factor (IGF)1 and the acid labile subunit and increased expression of an inhibitor, IGF-binding protein-1. The significance of these findings was demonstrated by smaller muscle fiber size in a model lacking myostatin and liver IGF1 expression (LID-o-Mighty mice) compared with that in myostatin-null (Mighty) mice. These data together suggest that myostatin may regulate pituitary development and function and that its inhibitory actions in muscle may be partly mediated by attenuating GH action in the liver. They also suggest that circulating pharmacological inhibitors of myostatin could produce unintended consequences in these and possibly other tissues.

IGF binding protein 5 and IGF-I receptor regulation in hypophysectomized rat kidneys

1994 ◽  
Vol 266 (1) ◽  
pp. F147-F154 ◽  
Author(s):  
M. K. Hise ◽  
N. M. Mantzouris ◽  
J. S. Lahn ◽  
M. S. Sheikh ◽  
Z. M. Shao ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Binding Protein ◽  
Affinity Labeling ◽  
Similar Data ◽  
Cortical Tissue ◽  
Factor I ◽  
Lower Molecular Mass ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

This study examines growth-regulating adaptations made by the proximal nephron in response to hypophysectomy (HYPX). Fourteen days after HYPX, circulating insulin-like growth factor I (IGF-I) levels were diminished, averaging 97 +/- 7 compared with 650 +/- 69 ng/ml in controls (n = 5, P < 0.001). Similar data were observed at day 7. Binding of 125I-IGF-I to isolated glomerular membranes and proximal tubule basolateral membranes (BLM) was increased in HYPX rats. Affinity labeling of membranes with 125I-IGF-I followed by electrophoresis on 6% polyacrylamide gels demonstrated two bands, one of approximately 140 kDa and another of > 200 kDa. The lower-molecular-mass protein, which has been identified as the alpha-subunit of the IGF-I receptor, and the higher-molecular-mass species were both upregulated by HYPX. Ligand blotting with IGF-I demonstrated a 31-kDa protein in both membranes, identified by immunostaining as IGF binding protein 5 (IGFBP-5), not IGFBP-1 or IGFBP-2. Affinity labeling documented an upregulation of this protein in both membranes after HYPX. Ligand blotting demonstrated a 31-kDa protein in HYPX cortical but not normal cortical or medullary cytosol that was immunostained with IGFBP-5 antibodies. RNA prepared from normal kidney cortical tissue demonstrated a 6.0-kb IGFBP-5 transcript, which was increased at day 14 after HYPX. Adaptations in the kidney after HYPX include an upregulation of the IGF-I receptor as well as IGFBP-5.(ABSTRACT TRUNCATED AT 250 WORDS)

An acid-stable insulin-like growth factor (IGF)-binding protein from pig serum inhibits binding of IGF-I and IGF-II to vascular endothelial cells

1989 ◽  
Vol 120 (2) ◽  
pp. 231-236 ◽  
Author(s):  
R. Gopinath ◽  
P. E. Walton ◽  
T. D. Etherton
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Binding Protein ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf Receptors ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Acid Stable

ABSTRACT The effects of a porcine insulin-like growth factor (IGF)-binding protein on binding of IGF-I and IGF-II to porcine aortic endothelial cells (PAEC) were determined. Binding of 125I-labelled IGF-I and -II to IGF receptors was inhibited by IGF-binding protein. IGF-binding protein inhibited binding of IGF-I and -II in a dose-dependent manner with half-maximal inhibition occurring at 5·43 and 108 μg/l respectively. A125I-labelled IGF-I–IGF-binding protein complex, formed by incubating 125I-labelled IGF-I with IGF-binding protein overnight at 4 °C, did not effectively bind to endothelial IGF receptors. Addition of IGF-binding protein to PAEC previously incubated with IGF-I caused a marked dissociation of bound IGF-I (47% dissociation within 12 h). These results indicate that the acid-stable IGF-binding protein which appears to be a part of the 150 kDa GH-dependent binding protein, blocks binding of IGF-I and -II by the IGF receptors and appears to exhibit a higher affinity for IGF-I than the endothelial type-I IGF receptor. The ramifications of this latter point with respect to transfer of circulating IGFs (bound to their IGF-binding proteins) across the vascular endothelium are not clear. Journal of Endocrinology (1989) 120, 231–236

scholarly journals An iTSC-derived placental model of SARS-CoV-2 infection unveils ACE2-dependent susceptibility in syncytiotrophoblasts

2021 ◽  
Author(s):  
Joseph Chen ◽  
Jessica A Neil ◽  
Jia Ping Tan ◽  
Raj Rudraraju ◽  
Monika Mohenska ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cell Types ◽  
Specific Cell ◽  
Placental Development ◽  
Health Crisis ◽  
Placental Cell ◽  
Trophoblast Stem Cells ◽  
Vitro Model ◽  
And Function

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has caused a global health crisis. The primary site of infection is in the respiratory tract but the virus has been associated with a variety of complications involving the gastrointestinal and cardiovascular systems. Since the virus affects a variety of tissue types, there has been interest in understanding SARS-CoV-2 infection in early development and the placenta. The expression of ACE2 or TMPRSS2, both genes critical for viral entry, is present in placental-specific cell types such as extravillous trophoblasts (EVTs) and, especially, syncytiotrophoblasts (STs). The potential of SARS-CoV-2 to infect these placental cells and its effect on placental development and function is still unclear. Furthermore, it is crucial to understand the possible mechanism of vertical transmission of SARS-CoV-2 through the placenta. Here, we developed an in vitro model of SARS-CoV-2 infection of placental cell types using induced trophoblast stem cells (iTSCs). This model allowed us to show that STs but not EVTs are infected. Importantly, infected STs lack the expression of key differentiation genes, lack typically observed differentiated morphology and produce significantly lower human chorionic gonadotropin (HCG) compared to non-infected controls. We also show that an anti-ACE2 antibody prevents SARS-CoV-2 infection and restores normal ST differentiation and function. We highlight the establishment of a platform to study SARS-CoV-2 infection in early placental cell types, which will facilitate investigation of antiviral therapy to protect the placenta during early pregnancy and development.

scholarly journals Transforming Growth Factor-β (TGFβ) Receptors I/II Differentially Regulate TGFβ1 and IGF-Binding Protein-3 Mitogenic Effects in the Human Placenta

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1723-1731 ◽  
Author(s):  
Karen Forbes ◽  
Benoit Souquet ◽  
Rebecca Garside ◽  
John D. Aplin ◽  
Melissa Westwood
Keyword(s):  
Transforming Growth Factor ◽  
Immunohistochemical Analysis ◽  
First Trimester ◽  
Signaling Molecules ◽  
Placental Development ◽  
Igf Binding Proteins ◽  
Tgfβ Receptors ◽  
Igf Binding ◽  
And Function ◽  
Igfbp 3

Maternal IGFs regulate cytotrophoblast proliferation and, thereby, placental growth and function. IGF bioavailability is controlled by IGF-binding proteins (IGFBPs); in placenta, IGFBP-3 is particularly abundant. In other systems, IGFBP-3 can regulate cellular events independently of IGFs; these effects are thought to be mediated by TGFβ receptors (TβR). We have examined IGFBP-3 regulation of IGF-dependent and -independent cytotrophoblast proliferation in first-trimester placental explants and the role of TβRII in mediating these effects. In the presence of IGFBP-3 (50 nm), IGF-induced (10 nm) proliferation (monitored by immunohistochemical analysis of Ki67 expression and bromodeoxyuridine incorporation) was significantly reduced (P &lt; 0.05). IGFBP-3 also reduced basal proliferation independently of IGF receptor signaling. Immunohistochemical analysis demonstrated that TGFβ signaling molecules [TGFβ receptor I (TβRI), TβRII, TβRV, Smad-2, and ERK] are expressed in syncytium and/or cytotrophoblast. TGFβ1 (10 ng/ml) enhanced cytotrophoblast proliferation and activated both Smad-2 and ERK-1/2, whereas IGFBP-3 activated only Smad-2. The function of both TGFβ1 and IGFBP-3 was attenuated by a TβRII function-blocking antibody and by small interfering RNA-mediated knockdown of TβRII (P &lt; 0.05); this was accompanied by a reduction in Smad-2 activation. This study demonstrates that both TGFβ1 and IGFBP-3 signal through TβRI/II to influence human cytotrophoblast proliferation. However, downstream pathways are distinct, because IGFBP-3 acts only through Smad-2, whereas TGFβ1 also phosphorylates ERK, resulting in opposite effects on cytotrophoblast proliferation. The effects of maternal growth signals on placental growth and function therefore depend on the balance of ligands, receptors, and signaling molecules at the syncytiotrophoblast surface. Therapeutic manipulation of this balance might offer a strategy to optimize placental development and pregnancy outcome.

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