TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis

Schiavinato, Josiane Lilian dos Santos; Oliveira, Lucila Habib Bourguignon; Araújo, Astolfo Gomes de Mello; Orellana, Maristela Delgado; Palma, Patrícia Viana Bonini; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

doi:10.1007/s11626-016-0055-8

Cited by 10 publications

(7 citation statements)

References 127 publications

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“…Following that cleavage, the TM domain is separated from NICD by γ secretase, allowing the NICD to translocate to the nucleus where it activates various transcription factors including Hey1 and Hes1(58-61). TNF-α has been shown to activate Notch signaling and increase the gene expression of transcription factors Hey and Hes1 in fibroblasts, nucleus pulposus cells, and melanoma cell lines(56, 61-63). We studied whether CCL2 and TNF-α activated ADAM0 by increasing activation of PC7 and furin through Notch1 mediated signaling by measuring the gene expression of Hes1 and Hey1.…”

Section: Discussionmentioning

confidence: 99%

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection

Megra

Eugenín

Berman

2017

The Journal of Immunology

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HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV infected people. The non-pathogenic cellular isoform of the human prion protein (PrPc) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrPc (sPrPc) is increased in the CSF of HIV infected people with cognitive deficits as compared to infected people with no impairment. Here we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV infected people, increase shedding of PrPc from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, as treatment of astrocytes with recombinant PrPc (recPrPc) increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from recPrPc treated astrocytes containing factors produced in response to this treatment, but not recPrPc by itself, cause increased chemotaxis of both uninfected and HIV infected human monocytes, suggesting a role for sPrPc in monocyte recruitment into the brain. Furthermore, we examined whether PrPc participates in glutamate uptake, and found that recPrPc decreased uptake of this metabolite in astrocytes, that could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrPc shedding, and the effect of this sPrPc on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrPc could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS.

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Section: Discussionmentioning

confidence: 99%

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection

Megra

Eugenín

Berman

2017

The Journal of Immunology

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“…The HOXB family involvement in tumor EMT has yet to be fully investigated, and EMT-associated HOXBs in OV have rarely been reported [18][19][20][21][22]. Homeobox B4 (HOXB4) is an important transcription factor involved in the progression of lung, breast, prostate, and bladder cancer [23][24][25][26][27]. HOXB4 enhances proliferation and the stat3 pathway [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Xiong²,

2020

Preprint

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Section: Introductionmentioning

confidence: 99%

HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Gou

Xiong

et al. 2020

Preprint

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Background : Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods : The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results : The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression. Conclusion : Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.

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TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis

Cited by 10 publications

References 127 publications

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection

HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

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