Density-Dependent Inhibition of Mouse Embryo Fibroblast Growth: Involvement of IGFBP-3

Blat, C.; Villaudy, J.; Harel, L

doi:10.1006/excr.1994.1322

Cited by 17 publications

(13 citation statements)

References 3 publications

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“…The PEC suspension obtained on days 3, 5, and 7 after the infection with 2 ϫ 10 4 PFU of MCMV on day 0 was incubated in a culture dish at 37°C for 45 min while changing the dish twice, and then nonadherent cells were obtained for use as effector cells. To prepare target cells, MCMV-infected primary mouse embryonic fibroblasts (MEFs) were prepared from C57BL/6 as described previously (39), and then labeled with 3.7 MBq 51 Cr (per ml) (40). The target cells and nonadherent PECs were mixed at various ratios in 0.2 ml RPMI 1640 on a V-bottom 96-well microplate and then incubated for 4 h at 37°C.…”

Section: Cytolytic Effector Cell Assaymentioning

confidence: 99%

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

Noda

Tanaka

Sawamura

et al. 2001

The Journal of Immunology

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Whether or not NO plays a critical role in murine CMV (MCMV) infection has yet to be elucidated. In this study, we examined the role of NO in acute infection with MCMV using NO synthase type 2 (NOS2)-deficient mice. NOS2−/− mice were more susceptible to lethal infection with MCMV than NOS2+/+ mice and generated a much higher peak virus titer in the salivary gland after acute infection. A moderate increase in the MCMV titer was also observed in other organs of NOS2−/− mice such as the spleen, lung, and liver. The immune responses to MCMV infection including NK cell cytotoxicity and CTL response in NOS2−/− mice were comparable with those of NOS2+/+ mice. Moreover, the ability to produce IFN-γ is not impaired in NOS2−/− mice after MCMV infection. The peritoneal macrophages from NOS2−/− mice, however, exhibited a lower antiviral activity than those from NOS2+/+ mice, resulting in an enhanced viral replication in macrophages themselves. Treatment of these cells from NOS2+/+ mice with a selective NOS2 inhibitor decreased the antiviral activity to a level below that obtained with NOS2−/− mice. In addition, the absence of NOS2 and NOS2-mediated antiviral activity of macrophages resulted in not only an enhanced MCMV replication and a high mortality but also a consequent risk of the latency. It was thus concluded that the NOS2-mediated antiviral activity of macrophages via NO plays a protective role against MCMV infection at an early and late stage of the infection.

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Section: Cytolytic Effector Cell Assaymentioning

confidence: 99%

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

Noda

Tanaka

Sawamura

et al. 2001

The Journal of Immunology

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“…This phenomena has been termed contact inhibition or density-dependent inhibition of cell growth (Blat et al, 1994;Stoker and Rubin, 1967). Several distinct mechanisms may mediate density-dependent inhibition of cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Homotypic cell contact-dependent inhibition of astrocyte proliferation

Nakatsuji

Miller

1998

Glia

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“…Endogenous BMP1-like Proteinases Play a Role in the Proteolytic Cleavage of Endogenous IGFBP3 in MEF Cultures-It has previously been demonstrated that IGFBP3 is secreted in MEF cultures (19). As can be seen ( Fig.…”

Section: Resultsmentioning

confidence: 68%

Bone Morphogenetic Protein-1 Processes Insulin-like Growth Factor-binding Protein 3

Kim

Huang

et al. 2011

Journal of Biological Chemistry

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The bone morphogenetic protein-1 (BMP1)-like metalloproteinases play key roles in extracellular matrix formation, by converting precursors into mature functional proteins involved in forming the extracellular matrix. The BMP1-like proteinases also play roles in activating growth factors, such as BMP2/4, myostatin, growth differentiation factor 11, and transforming growth factor ␤1, by cleaving extracellular antagonists. The extracellular insulin-like growth factor-binding proteins (IGFBPs) are involved in regulating the effects of insulin-like growth factors (IGFs) on growth, development, and metabolism. Of the six IGFBPs, IGFBP3 has the greatest interaction with the large pool of circulating IGFs. It is also produced locally in tissues and is itself regulated by proteolytic processing. Here, we show that BMP1 cleaves human and mouse IGFBP3 at a single conserved site, resulting in markedly reduced ability of cleaved IGFBP3 to bind IGF-I or to block IGF-I-induced cell signaling. In contrast, such cleavage is shown to result in enhanced IGF-Iindependent ability of cleaved IGFBP3 to block FGF-induced proliferation and to induce Smad phosphorylation. Consistent with in vivo roles for such cleavage, it is shown that, whereas wild type mouse embryo fibroblasts (MEFs) produce cleaved IGFBP3, MEFs doubly null for the Bmp1 gene and for the Tll1 gene, which encodes the related metalloproteinase mammalian Tolloid-like 1 (mTLL1), produce only unprocessed IGFBP3, thus demonstrating endogenous BMP1-related proteinases to be responsible for IGFBP3-processing activity in MEFs. Similarly, in zebrafish embryos, overexpression of Bmp1a is shown to reverse an Igfbp3-induced phenotype, consistent with the ability of BMP1-like proteinases to cleave IGFBP3 in vivo.Bone morphogenetic protein-1 (BMP1)-like proteinases affect morphogenetic events via biosynthetic processing of precursors into mature functional proteins involved in forming the extracellular matrix. Extracellular matrix-related substrates include precursors for collagens I-III, V, VII, and XI; the crosslinking enzyme lysyl oxidase; proteoglycans biglycan and osteoglycin; and basement membrane component laminin-332 (laminin-5) (1). These proteinases are also involved in the biosynthetic processing that produces peptides involved in initiating the mineralization of bones and teeth and in processing the hormone prolactin and the proteoglycan perlecan to produce anti-angiogenic factors (1, 2). In addition, BMP1-like proteinases are involved in activating extracellular latent complexes of some transforming growth factor ␤ (TGF␤) superfamily members, including BMP2, BMP4, growth and differentiation factor 8 (GDF8) (also known as myostatin), GDF11, and TGF␤1 (1, 3).Insulin-like growth factors, IGF-I 2 and -II, are evolutionarily conserved polypeptide growth factors with important effects on mitogenesis, development, somatic growth, and metabolism (4). In extracellular spaces and in biological fluids, IGFs are normally bound to a family of IGF-binding proteins (IGFBPs), which modu...

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Density-Dependent Inhibition of Mouse Embryo Fibroblast Growth: Involvement of IGFBP-3

Cited by 17 publications

References 3 publications

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

Homotypic cell contact-dependent inhibition of astrocyte proliferation

Bone Morphogenetic Protein-1 Processes Insulin-like Growth Factor-binding Protein 3

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