Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis through Increased Urokinase Expression

Colombo, E.; Menicucci, G.; McGuire, Paul; Das, Arup

doi:10.1167/iovs.06-0923

Cited by 44 publications

(31 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Vascular endothelial growth factor (VEGF) is the growth factor of primary importance in driving the angiogenic process forward in most tissues. 45 VEGF interacting with its receptor VEGFR-2 rapidly induces prourokinase (pro-u-PA) activation on the surface of endothelial cells, which involves a phosphatidylinositol 3-kinase (PI3k)-dependent change in integrin affinity. 46,47 A large body of experimental evidence from in vitro and in vivo studies indicates that, in VEGFinduced endothelial cell migration and angiogenesis, the u-PA/u-PAR system, especially the presence of u-PAR, seems to be essential, because their inhibition can result in the significant decrease of tumor neovascularization.…”

Section: Discussionmentioning

confidence: 99%

RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo

Zhou

Tang

Liang

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

It has been admitted that urokinase-type plasminogen activator receptor (u-PAR) is overexpressed in many human malignant tumors including oral squamous cell carcinoma (OSCC) and plays an important role in a variety of cancer key cellular events as a versatile signaling orchestrator. In our study, a retroviral vector expressing u-PAR-specific siRNA was injected into OSCC xenografts of nude mice to observe its inhibitory effects on OSCC. Our data demonstrate that siRNA targeting u-PAR markedly suppressed tumor growth, reduced the expression of proliferation-related gene, Ki-67 and increased cell apoptosis, accompanying with the efficient and specific inhibition of endogenous u-PAR expression in OSCC. More importantly, the mRNA and protein expression of MMP-2, MMP-9, VEGF-C, VEGF-D and VEGFR-3 that are intimately involved in oral cancer invasion and metastasis, was simultaneously downregulated significantly as determined by quantitative real-time RT-PCR, Western blot and immunohistochemistry; and Gelatin and fibrin zymography showed that MMP-9, MMP-2 and u-PA enzymatic activities were significantly reduced in u-PAR-specific siRNA group, compared to those in control groups. In addition, the expression of MDR-1 gene related to drug resistance was obviously inhibited by silencing of u-PAR. These findings suggest that RNAi targeting u-PAR could effectively inhibit the metastasis and progression of OSCC in vivo. Thus, it may be used as a potent and specific therapy for oral cancer, especially in inhibiting and preventing cancer cell invasion and metastasis. ' UICCKey words: RNA interference; urokinase-type plasminogen activator receptor; oral squamous cell carcinoma; metastasis; cancer progression Oral squamous cell carcinoma (OSCC) accounts for about 80% of all oral malignant tumors. The 5-year survival rate for patients with OSCC was still poor, approximately 56%, despite advances in chemotherapy, radiotherapy and surgical therapy in the past 20 years.1,2 The relatively high mortality of OSCC is predominantly associated with widespread lymphatic and distant metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo

Zhou

Tang

Liang

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…This includes not only mild infiltration of macrophages and accumulation of microglia, but also the presence of inflammatory components such as complement factors, pro-inflammatory cytokines, and chemokines. Many growth factors have been shown to be involved in the development of retinal neovascularization, including vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), basic fibroblast growth factor (bFGF, FGF-2), hepatocyte growth factor (HGF), tumor necrosis factor alpha (TNF-α), and others (Kwak et al, 2000; Spilsbury et al, 2000; Lip et al, 2001; Amin et al, 1994; Tomita et al, 2003; Colombo et al, 2007; Qazi et al, 2009; Hu et al, 2009; Dias et al, 2011). A study of genetic linkage and allelic association has identified VEGF, low density lipoprotein receptor-related protein 6 (LRP6) and very low-density lipoprotein receptor (VLDLR) as candidate genes in AMD (Haines et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice

Kyosseva

Chen

Seal

et al. 2013

Experimental Eye Research

View full text Add to dashboard Cite

Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The Very Low-Density Lipoprotein Receptor knockout mouse (Vldlr−/−) has been identified as a model for AMD and in particular for Retinal Angiomatous Proliferation (RAP). In this study we examined the effect of cerium oxide nanoparticles (nanoceria) that have been shown to have catalytic antioxidant activity, on expression of 88 major cytokines in the retinas of Vldlr−/− mice using a PCR array. A single intravitrial injection of nanoceria at P28 caused inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors including Tslp, Lif, Il-3, Il-7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna 3, Lep, and up-regulation of several cytokines and anti-angiogenic genes in the Vldlr−/−retina within one week. We used the Ingenuity Pathway Analysis software to search for biological functions, pathways, and interrelationships between gene networks. Many of the genes whose activities were affected are involved in cell signaling, cellular development, growth and proliferation, and tissue development. Western blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. These data suggest that nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases.

show abstract

“…кроме того, Vegf стимулирует экспрессию урокиназы в сосуди-стых эндотелиальных клетках [167]. Ангиоге-нез в сетчатке, индуцированный hgf, также опосредован увеличением активности уроки-назы [168]. нарушение взаимодействия уро-киназы с ее рецептором ингибирует усиление миграционной и инвазивной активности эн-дотелиальных клеток под действием hgf.…”

Section: рис 11 механизмы регуляции роста и ремоделирования артерийunclassified

Role of multidomain structure of urokinase in regulation of growth and remodeling of vessels

Ткачук¹

2013

Ukr.Biochem.J.

View full text Add to dashboard Cite

Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis through Increased Urokinase Expression

Abstract: These studies suggest that HGF may play an important role in the initial stages of retinal angiogenesis by stimulating a migratory phenotype in endothelial cells mediated by increased urokinase activity.

Cited by 44 publications

References 47 publications

RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo

RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo

Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice

Role of multidomain structure of urokinase in regulation of growth and remodeling of vessels

Contact Info

Product

Resources

About