Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading

Fraga, Carlos Alberto de Carvalho; Farias, Lucyana Conceição; Oliveira, Marcos Vinícius Macedo de; Domingos, Patrícia Luciana Batista; Pereira, Camila Santos; Silva, Thiago Fonseca; Roy, Amrita; Gomez, Ricardo Santiago; Paula, Alfredo Maurício Batista de; Guimarães, André Luiz Sena

doi:10.1016/j.prp.2014.06.020

Cited by 22 publications

(23 citation statements)

References 46 publications

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“…Furthermore, MMP-9 and VEGFR2 showed positive correlations during epithelial dysplasia in oral leukoplakia. 38 Our results showed that the expression of VEGFR2 increased in HRE-MMP-9 mice compared to other groups of mice, which supported that MMP-9 promoted angiogenesis after ischemic injury by the VEGF/VEGFR2 signaling pathway. Additionally, MMP-9 is essential for ischemia-induced neovascularization by recruiting and mobilizing bone-marrowderived EPCs.…”

Section: Discussionsupporting

confidence: 76%

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke

Cai

Jiang

et al. 2017

Molecular Therapy

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Matrix metalloproteinase 9 (MMP-9) plays a beneficial role in the delayed phase of middle cerebral artery occlusion (MCAO). However, the mechanism is obscure. Here, we constructed hypoxia response element (HRE)-regulated MMP-9 to explore its effect on glial scars and neurogenesis in delayed ischemic stroke. Adult male Institute of Cancer Research (ICR) mice underwent MCAO and received a stereotactic injection of lentivirus carrying HRE-MMP-9 or normal saline (NS)/lentivirus-GFP 7 days after ischemia. We found that HRE-MMP-9 improved neurological outcomes, reduced ischemia-induced brain atrophy, and degraded glial scars (p < 0.05). Furthermore, HRE-MMP-9 increased the number of microvessels in the peri-infarct area (p < 0.001), which may have been due to the accumulation of endogenous endothelial progenitor cells (EPCs) in the peri-infarct area after glial scar degradation. Finally, HRE-MMP-9 increased the number of bromodeoxyuridine-positive (BrdU)/NeuN cells and the expression of PSD-95 in the peri-infarct area (p < 0.01). These changes could be blocked by vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor SU5416 and MMP-9 inhibitor 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT). Our results provided a novel mechanism by which glial scar degradation and vascular endothelial growth factor (VEGF)/VEGFR2-dependent angiogenesis may be key procedures for neurological recovery in delayed ischemic stroke after HRE-MMP-9 treatment. Therefore, HRE-MMP-9 overexpression in the delayed ischemic brain is a promising approach for neurological recovery.

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Section: Discussionsupporting

confidence: 76%

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke

Cai

Jiang

et al. 2017

Molecular Therapy

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“…It is known in the literature that angiogenesis (MVD) significantly increases from normal oral mucosa to epithelial dysplasia to oral squamous cell carcinoma . Moreover, previous studies have shown increase in angiogenesis from NOM through various grades of OED . The angiogenic switch occurs in the dysplastic stage preceding tumor development in the hamster cheek pouch model of oral cancer .…”

Section: Discussionmentioning

confidence: 93%

“…18,19 Moreover, previous studies have shown increase in angiogenesis from NOM through various grades of OED. 20,21 The angiogenic switch occurs in the dysplastic stage preceding tumor development in the hamster cheek pouch model of oral cancer. 22 In potentially malignant tissues, increased vascular endothelial growth factor expression favors endothelial cell proliferation and an increase in vascular density.…”

Section: Discussionmentioning

confidence: 99%

Ki67, CD105, and α‐SMA expressions better relate the binary oral epithelial dysplasia grading system of World Health Organization

Gadbail

Chaudhary

Sarode

et al. 2017

J Oral Pathology Medicine

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“…MMPs occur in human samples, which can be evaluated by immunohistochemistry, enzyme-linked immunosorbent assays (ELISA), zymography and real-time polymerizing chain reaction. Immunohistochemistry is the most commonly used methodology in tissue samples,[ 12 15 16 17 18 19 ] which has not quantified the MMP-9 levels, it also cannot differentiate between the latent and active forms of MMP. In serum sample, only a single study has been done in which MMP-9 is quantified by ELISA,[ 14 ] which is sensitive but expensive.…”

Section: Discussionmentioning

confidence: 99%

Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review

Venugopal

Maheswari

2016

J Oral Maxillofac Pathol

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Matrix metalloproteinase-9 (MMP-9) is an inducible enzyme. Oral potentially malignant disorders (OPMDs) are considered as the early tissue changes that happen due to various habits such as smoking tobacco, chewing tobacco or stress. This alteration in the tissues alters the expression of MMP-9. The rationale of the review is to know the expression of MMP-9 in OPMDs. Hand searching and electronic databases such as PubMed and ScienceDirect were done for mesh terms such as OPMDs and MMP-9. Eight articles were obtained, after applying inclusion and exclusion criteria. These articles were assessed with QUADAS and data were extracted and evaluated. The included eight studies were done in 182 oral squamous cell carcinoma cases, 430 OPMDs (146 oral lichen planus, 264 leukoplakia and 20 oral submucous fibrosis) and 352 healthy controls evaluated for MMP-9. MMP-9 expression was found to be elevated in tissue, serum and saliva samples of OPMDs than in healthy controls. There is only one study in each serum and saliva samples to evaluate MMP-9. Saliva being noninvasive and serum being minimally invasive, more studies need to be done in both serum and saliva to establish MMP-9 as an early diagnostic marker in OPMDs to know its potential in malignant transformation.

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Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading

Cited by 22 publications

References 46 publications

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke

Ki67, CD105, and α‐SMA expressions better relate the binary oral epithelial dysplasia grading system of World Health Organization

Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review

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