Spaceflight modulates insulin-like growth factor binding proteins and glucocorticoid receptor in osteoblasts

1998 ◽  
Vol 85 (1) ◽  
pp. 139-147 ◽  
Author(s):  
Yasuhiro Kumei ◽  
Hitoyata Shimokawa ◽  
Hisako Katano ◽  
Hideo Akiyama ◽  
Masahiko Hirano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucocorticoid Receptor ◽  
Space Shuttle ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Dihydroxyvitamin D ◽  
Protein Levels ◽  
Glucocorticoid Receptor Mrna ◽  
Cellular Dna

Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission. After 20-h treatment with 1α,25-dihydroxyvitamin D3, conditioned media were harvested and cellular DNA and/or RNA were fixed on board. The insulin-like growth factor binding protein (IGF BP)-3 levels in the media were three- and tenfold higher than in ground controls on the fourth and fifth flight days, as quantitated by Western ligand blotting and radioimmunoassay, respectively. The increased IGF BP-3 protein levels correlated with two- to threefold elevation of IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain reaction. The IGF BP-5 mRNA levels in flight cultures were 33–69% lower than in ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than in ground controls on the fifth day but were not different on the fourth day. The glucocorticoid receptor mRNA levels in flight cultures were increased by three- to eightfold on the fourth and fifth days compared with levels in ground controls. These data suggest potential mechanisms underlying spaceflight-induced osteopenia.

scholarly journals Insulin-Like Growth Factor Binding Protein 6 Is Secreted in Extracellular Vesicles upon Hyperthermia and Oxidative Stress in Dendritic Cells But Not in Monocytes

2020 ◽  
Vol 21 (12) ◽  
pp. 4428
Author(s):  
Massimo Conese ◽  
Lorenzo Pace ◽  
Nicoletta Pignataro ◽  
Lucia Catucci ◽  
Antonio Ambrosi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Growth Factor ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Protein Levels ◽  
Inflammatory Stimuli ◽  
And Oxidative Stress

Recently, insulin-like growth factor binding protein 6 (IGFBP-6) has been shown to play a putative role in the immune system, as monocyte-derived dendritic cells (Mo-DCs) are stimulated by hyperthermia to express IGFBP-6 at both the mRNA and protein levels. However, the presence of IGFBP-6 in extracellular vesicles (EVs) and whether other pro-inflammatory stimuli can induce IGFBP-6 expression in Mo-DCs are not known yet. In this brief report, we show that hyperthermia (39 °C) induces IGFBP-6 secretion associated with microvesicles and exosomes as early as 3 h. Moreover, free IGFBP-6 is found in conditioned media (CM) of hyperthermia- and H2O2-treated Mo-DCs, but not in CM obtained from monocytes similarly treated. These results show that diverse inflammatory stimuli can induce IGFBP-6 association with EVs and secretion in conditioned medium, indicating a role for IGFBP-6 in communication between immune cells.

scholarly journals Insulin-like Growth Factor II Signaling in Neoplastic Proliferation Is Blocked by Transgenic Expression of the Metalloproteinase Inhibitor Timp-1

1999 ◽  
Vol 146 (4) ◽  
pp. 881-892 ◽  
Author(s):  
David C. Martin ◽  
John L. Fowlkes ◽  
Bojana Babic ◽  
Rama Khokha
Keyword(s):  
Growth Factor ◽  
T Antigen ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Early Event ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Protein Levels ◽  
Igf I ◽  
Igfbp 3

Insulin-like growth factor (IGF) II is overexpressed in many human cancers and is reactivated by, and crucial for viral oncogene (SV40 T antigen, [TAg])–induced tumorigenesis in several tumor models. Using a double transgenic murine hepatic tumor model, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP-1) blocks liver hyperplasia during tumor development, despite TAg-mediated reactivation of IGF-II. Because the activity of IGFs is controlled by IGF-binding proteins (IGFBPs), we investigated whether TIMP-1 overexpression altered the IGFBP status in the transgenic liver. Ligand blotting showed that IGFBP-3 protein levels were increased in TIMP-1–overexpressing double transgenic littermates, whereas IGFBP-3 mRNA levels were not different, suggesting that TIMP-1 affects IGFBP-3 at a posttranscriptional level. IGFBP-3 proteolysis assays demonstrated that IGFBP-3 degradation was lower in TIMP-1–overexpressing livers, and zymography showed that matrix metalloproteinases (MMPs) were present in the liver homogenates and were capable of degrading IGFBP-3. As a consequence of reduced IGFBP-3 proteolysis and elevated IGFBP-3 protein levels, dissociable IGF-II levels were significantly lower in TIMP-1–overexpressing animals. This decrease in bioavailable IGF-II ultimately resulted in diminished IGF-I receptor signaling in vivo as evidenced by diminished receptor kinase activity and decreased tyrosine phosphorylation of the IGF-I receptor downstream effectors, insulin receptor substrate 1 (IRS-1), extracellular signal regulatory kinase (Erk)-1, and Erk-2. Together, these results provide evidence that TIMP-1 inhibits liver hyperplasia, an early event in TAg-mediated tumorigenesis, by reducing the activity of the tumor-inducing mitogen, IGF-II. These data implicate the control of MMP-mediated degradation of IGFBPs as a novel therapy for controlling IGF bioavailability in cancer.

Decreased insulin-like growth factor binding protein-4 (IGFBP-4) mRNA levels in the liver after hypophysectomy

1994 ◽  
Vol 150 (2) ◽  
pp. 235-237
Author(s):  
J. PINEDA ◽  
R. COYA ◽  
G. JACOBSSON ◽  
M. LAKE ◽  
K. HALL ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals The Prognostic Values of the Insulin-Like Growth Factor Binding Protein Family in Ovarian Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Ruoyi Zheng ◽  
Wenming Chen ◽  
Weiting Xia ◽  
Jingyu Zheng ◽  
Qing Zhou
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Protein Expression ◽  
Mrna Expression ◽  
Binding Protein ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Factor Binding

Purpose. To assess the expression of insulin-like growth factor binding protein (IGFBP) family and its prognostic impact in ovarian cancer (OC) patients. Materials and Methods. The mRNA expression and protein expression of individual IGFBPs in healthy ovarian samples and OC tissues were explored through Oncomine, Gene Expression Profiling Interactive Analysis, and Human Protein Atlas database. Additionally, the prognostic values of the six IGFBP members in patients with OC were evaluated by Kaplan-Meier plotter. Results. IGFBP2 and IGFBP4 mRNA expression were remarkably upregulated in patients with OC. To be specific, the mRNA expression of IGFBP2 was upregulated in patients with serous ovarian cancer (SOC), while IGFBP1/3/4/5/6 mRNA levels were downregulated. In addition, the IGFBP4 protein expression was upregulated in SOC, and the IGFBP6 protein expression was upregulated in both of SOC and endometrioid ovarian cancer (EOC) tissues. High IGFBP1 mRNA levels showed favorable overall survival (OS) and progression-free survival (PFS) in all OC. Meanwhile, increased IGFBP5/6 mRNA levels revealed worsen OS and PFS in all OC patients. IGFBP4/6 mRNA levels predicted unfavorable OS and PFS only in SOC patients. Moreover, the aberrant mRNA expression of IGFBP1/2/4/5/6 was correlated with significantly prognosis in patients receiving different chemotherapeutic regimens. Conclusion. This study indicates that the IGFBP family reveals distinct prognosis in patients with OC. IGFBP1/2/4/5/6 are useful prognostic predictors for chemotherapeutic effect in OC patients, and IGFBP2/4 are potential tumor markers for the diagnosis of OC.

scholarly journals Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells

1999 ◽  
Vol 163 (2) ◽  
pp. 281-288 ◽  
Author(s):  
P Andersson ◽  
T Gustafsson ◽  
HJ Arnqvist
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Binding Proteins ◽  
Muscle Cells ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Factor Binding

We have investigated the expression and secretion of insulin-like growth factor binding proteins (IGFBPs-1 to -6) in human vascular smooth muscle cells (hVSMCs) cultured from human renal arteries. Solution hybridization was used to determine IGFBP mRNA levels and Western immunoblot to detect the corresponding peptides. The hVSMCs expressed mRNAs for IGFBPs-2 to -6; IGFBP-1 mRNA was not detected. IGFBPs-3, -4 and -6 mRNAs were the most abundant, IGFBP-5 was also highly expressed, whereas the IGFBP-2 mRNA was just above the limit of detection. Serum starvation for 48 h significantly decreased the mRNA levels of IGFBPs-2 to -5 and tended to decrease IGFBP-6 mRNA also. IGFBPs-2, -4, -5 and -6 peptides could be detected in conditioned medium, but IGFBP-3 peptide was not detected. IGFBP-4 was the only peptide detected without any concentration step. Low-molecular-mass immunoreactive degradation products were found for IGFBPs-2 and -4. Exogenous IGFBPs-1, -3 and -4 in concentrations of 50 ng/ml inhibited DNA synthesis induced by 1 nM IGF-I, whereas IGFBPs-2, -5 and -6 had no significant inhibitory effects at this concentration. We conclude from these results that all IGFBPs except IGFBP-1 are expressed in hVSMC. Our results indicate that locally produced, in addition to circulating, IGFBPs may have an important role in the regulation of hVSMC.

Messenger RNA levels of growth factors, ligands, receptors, and proteins affecting lipid metabolism in pigs

2000 ◽  
Vol 80 (4) ◽  
pp. 559-567 ◽  
Author(s):  
Claude Robert ◽  
Marie-France Palin ◽  
Frederick G. Silversides ◽  
Robert M. Mckay ◽  
Ghislain Pelletier
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Low Density Lipoprotein ◽  
Growth Factor Receptor ◽  
Density Lipoprotein ◽  
Backfat Thickness ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Density Lipoprotein Receptor

The Northern blot technique was used for mRNA phenotyping of 19 growth factors, ligands, receptors, and proteins involved in lipid metabolism in two populations of pigs with different fat deposition capabilities. The mRNA levels were measured in backfat, liver, and muscle tissue at different slaughter weights, taking backfat thickness, gender and breed of the animals into consideration. Of all the RNA patterns measured in the Landrace population, only the mRNA transcript level of low density lipoprotein receptor-related protein (also called alpha 2-macroglobulin receptor) was associated with the pig's backfat thickness phenotype in muscle and backfat tissues. In the population composed of purebred Yorkshire and Hampshire, epidermal growth factor receptor, malic enzyme, platelet derived growth factor β and insulin-like growth factor binding protein 3 show different mRNA patterns associated with backfat thickness phenotypes. When analyzing the data using the gender or the breed as the main effect, the insulin receptor and insulin-like growth factor binding protein 1 were different between genders whereas insulin-like growth factor binding protein 3, malic enzyme, epidermal growth factor receptor and low density lipoprotein receptor-related protein were different between breeds. Analysis of this type should be helpful in understanding the regulation of fat deposition. Key words: mRNA levels, marker genes, backfat, pig

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