JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation

Zhang, Guishui; Fahmy, Roger G.; DiGirolamo, Nick; Khachigian, Levon M.

doi:10.1242/jcs.03059

Cited by 22 publications

(14 citation statements)

References 31 publications

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“…3A, 3B, 3C, and 5D). Interestingly, MMP-2 is under the transcriptional control of both c-Jun (14,31) and Egr-1 (32), suggesting that these and other nuclear factors control the same genes in a coordinated manner. Control of one important injury-and shear-responsive transcription factor by another suggests the existence of transcriptional amplification waves that magnify the signaling burst after acute cellular stress.…”

Section: Discussionmentioning

confidence: 99%

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

Waldman

Khachigian

2010

Journal of Biological Chemistry

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Coronary artery bypass graft failure represents an unsolved problem in interventional cardiology and heart surgery. Late occlusion of autologous saphenous vein bypass grafts is a consequence of neointima formation underpinned by smooth muscle cell (SMC) migration and proliferation. Poor long term patency and the lack of pharmacologic agents that prevent graft failure necessitate effective alternative therapies.

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Section: Discussionmentioning

confidence: 99%

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

Waldman

Khachigian

2010

Journal of Biological Chemistry

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“…There are several studies focusing on the role of jun family members in MMP2 induction in various types of cells. Generally, mitogen-activated protein kinases, including c-Jun NH 2 -terminal kinase, extracellular stress-regulated kinase, and the dependent transactivation of AP-1, lead to increased expression of MMP2 (49,50); therefore, it is reasonable that junB as the antagonist to c-Jun might suppress tumor cell invasion through MMP2 inhibition as seen in the current study. We already surmised that p16 was a downstream target of junB, because our data supported this.…”

Section: Discussionmentioning

confidence: 58%

Function of JunB in Transient Amplifying Cell Senescence and Progression of Human Prostate Cancer

Konishi¹,

Shimada²,

Nakamura³

et al. 2008

Clinical Cancer Research

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Purpose: Replicative senescence in cells acts as a barrier against excessive proliferation and carcinogenesis. Transient amplifying cells (TAC) are a subset of basal cell populations within the prostate from which cancers are thought to originate; therefore, we focused on prostate TAC to investigate the molecular mechanisms by which theTAC may be able to evade senescence. Experimental Design: TAC clones were isolated from each zone within the whole prostate and analyzed in flow cytometry. Prostate cancer cells were transfected with junB small interfering RNA (siRNA) and examined by chorioallantoic membrane assay for cancer invasion. Immunohistochemical analysis was done in primary and metastatic prostate cancer specimens. Results: TAC populations showed increased expression of p53, p21, p16, and pRb, resulting in senescence. TAC clones with reduced p16 expression successfully bypassed this phase. We further found close correlation between the levels of junB and p16 expression. Repeated transfection of junB siRNA in prostaticTAC allowed the cells to escape senescence presumably through inactivation of p16/pRb. The chorioallantoic membrane invasion assay showed much lower in invasive cancer cells with high expression of junB; conversely, silencing of junB by transfection with junB siRNA promoted invasion.We also found that metastatic prostate cancers, as well as cancers with high Gleason scores, showed significantly low junB immunopositivity. Conclusions: JunB is an essential upstream regulator of p16 and contributes to maintain cell senescence that blocks malignant transformation of TAC. JunB thus apparently plays an important role in controlling prostate carcinogenesis and may be a new target for cancer prevention and therapy.

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“…In accord with these findings, there is clear evidence that the redox-sensitive transcription factor c-Jun is up-regulated in response to either oxidants or oxidative stress (Kunsch and Medford, 1999, Lee et al, 1996). c-Jun is also associated with vascular dysfunction, including enhanced vascular remodeling and permeability, and inflammatory responses (Lum and Roebuck, 2001, Rojas et al, 2006), as well as with pathological angiogenesis and microvascular diseases in humans (Fahmy et al, 2006, Folkman, 2004, Zhang et al, 2004, Zhang et al, 2006). Interestingly, the up-regulation of c-Jun consequent to KRIT1 loss-of-function is accompanied by the induction of cycloxygenase 2 (COX-2), a major oxidative stress biomarker and inflammatory mediator involved in vascular dysfunctions (Hsieh et al, 2012, Ushio-Fukai and Nakamura, 2008), raising the possibility that KRIT1 loss-of-function might be implicated in synergistic oxidative stress and inflammatory responses (Goitre et al, 2014).…”

Section: Redox Signaling and Oxidative Stress: The Two Emerging Facesmentioning

confidence: 99%

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

Retta

Glading

2016

The International Journal of Biochemistry & Cell Biology

110

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Graphical abstractTowards a unifying mechanism for CCM disease pathogenesis and treatment.CCM proteins play pleiotropic roles in distinct redox-sensitive pathways by modulating the fine-tuned crosstalk between redox signaling and autophagy. Effective autophagy removes ROS-generating cellular trash, including damaged mitochondria, to rejuvenate cell environment, thus serving a cytoprotective function for the maintenance of endothelial cell monolayer integrity and functionality and blood–brain barrier (BBB) stability even under adverse stress conditions. Loss-of-function of a CCM protein (e.g., KRIT1) causes defective autophagy and altered redox signaling, affecting BBB stability and sensitizing endothelial cells to local oxidative stress and inflammatory events, which may act as key pathogenic determinants of focal formation and progression of CCM lesions. The common capacity to modulate the interplay between autophagy and redox signaling reconciles the distinct pharmacological approaches proposed so far for CCM disease prevention and treatment.

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JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation

Abstract: SummaryJUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation

Cited by 22 publications

References 31 publications

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins

Function of JunB in Transient Amplifying Cell Senescence and Progression of Human Prostate Cancer

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

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