Overexpression of human osteopontin increases cell proliferation and migration in human embryo kidney-293 cells

Liu, Yajun; Zhang, Daoqiang; Sui, Xiu-Mei; Tian, Wei

doi:10.2478/s11658-009-0027-z

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…The final configuration of the protein thus influences its bioactivity. Although OPN performs beneficial functions, it has also been linked to cancer-associated mechanisms, such as tumorigenesis and proliferation (Liu et al, 2009), which may explain the metastatic ability of cancer cells.…”

Section: Proteomic Analysis and Immunodetection Of The Bovine Milk Osteopontin Isoformsmentioning

confidence: 99%

Proteomic analysis and immunodetection of the bovine milk osteopontin isoforms

Bissonnette

Dudemaine

Thibault

et al. 2012

Journal of Dairy Science

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The aim of this study was to characterize the osteopontin (OPN) secreted in bovine milk and to determine whether the different forms are the product of spliced variants. Spliced variants of the human gene and secreted osteopontin isoforms have been reported in human tumor tissue. In bovine milk, we identified 2 major forms: one corresponding to the full-length coding transcript and a truncated version of this form. No alternative spliced transcripts were detected in the lactating mammary gland tissue, in milk somatic cells, or in peripheral blood immune cells. The 60-kDa bovine osteopontin (bOPN) and a truncated 40-kDa protein isoform were confirmed by mass spectrometry and further characterized by immunoblotting using a panel of 6 antibodies targeting different domains of the protein. Of the 3 human anti-OPN antibodies targeting the N-terminal segment of the protein, only one detected all forms on sodium dodecyl sulfate-PAGE; one human anti-OPN antibody failed to detect bOPN, whereas the other detected only the 60-kDa protein, albeit barely in its phosphorylated form. Detection was generally more sensitive when the 60-kDa protein was dephosphorylated. Two polyclonal antibodies raised against bOPN were tested: one targeting the milk-purified bOPN (bOPN-121) and one targeting a bovine epitope (synthetic peptide) corresponding to a carboxy-terminal domain of the protein (bOPN-117). The bOPN-121 antibody detected all forms irrespective of the phosphorylation status of bOPN. The bOPN-117 and the mouse anti-human OPN (hOPN-4) antibodies, which recognized different domains of the carboxy-terminal segment of the protein, also preferentially detected the dephosphorylated 60-kDa protein. Whereas phosphorylation had a major effect on detection for several antibodies, deglycosylation slightly decreased immunodetection for the tested antibodies. In particular, phosphorylation is the major posttranslational modification that influenced the weak detection capacity of several antibodies. This fact needs to be taken into account for immunodetection of milk content. In conclusion, the OPN forms secreted in bovine milk are not the product of alternative splicing. The 40-kDa protein appears to be a truncated hypophosphorylated variant of the full-length 60-kDa form, which is highly phosphorylated. Together, the proteomic and immunoblotting analyses used to characterize bovine milk OPN revealed the complex nature of the bovine milk OPN forms.

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Section: Proteomic Analysis and Immunodetection Of The Bovine Milk Osteopontin Isoformsmentioning

confidence: 99%

Proteomic analysis and immunodetection of the bovine milk osteopontin isoforms

Bissonnette

Dudemaine

Thibault

et al. 2012

Journal of Dairy Science

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“…The significant increase of PCNA expression in the spleen of AQtreated animals suggests activation of immune system, and there was also an increase in serum osteopontin. Recent studies have shown that osteopontin is not only able to enhance cell proliferation in many tissues such as kidney, and prostate (Angelucci et al 2004;Liu et al 2009), but it also plays an important role in mediating hepatic inflammation and the ensuing liver toxicity (Ramaiah et al 2007). In addition, osteopontin was reported to be closely related to production of IL-17, a pro-inflammatory cytokine, during the pathogenesis of chronic hepatitis B and concanavalin A-induced hepatitis (Diao et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Exploring an animal model of amodiaquine-induced liver injury in rats and mice

Liu

Cai

Metushi

et al. 2016

Journal of Immunotoxicology

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Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4(+) T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.

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“…OPN siRNA decreases mammary cell motility in vitro [147]. There is also evidence that OPN is capable of enhancing proliferation of various cell lines [155,156].…”

Section: Osteopontinmentioning

confidence: 99%