Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

Chintala, Hemabindu; Li, Haibo; Parmar, Rahul; Kamalska, Monika; Kim, Inah; Lovett, David H.; Grant, Maria B.; Chaqour, Brahim

doi:10.1074/jbc.m112.386565

Cited by 44 publications

(43 citation statements)

References 67 publications

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“…Rhabdovirus vesicular stomatitis virus (VSV-G)-pseudotyped lentiviral vectors were produced by transfection of 20 ϫ 150-mm plates of 293T cells with the following three plasmids: the helper packaging construct pCM-VDR8.2, the transfer vector, and the plasmid encoding for envelope protein VSV-G using the calcium phosphate precipitation method. The proportion of retinal cells transduced with lentiviral particles in a series of random sections (6 -12) that spanned at least 50% of the retinal surface varied between 45 and 79% (32). The Gene Therapy Resource Program of the NHLBI, National Institutes of Health, produced the gene vectors used in this study.…”

Section: Generation Of Ccn1 Deletion Mutants and Recombinant Adenovirmentioning

confidence: 99%

Degradome Products of the Matricellular Protein CCN1 as Modulators of Pathological Angiogenesis in the Retina

Choi

Lin

Shrier

et al. 2013

Journal of Biological Chemistry

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Section: Generation Of Ccn1 Deletion Mutants and Recombinant Adenovirmentioning

confidence: 99%

Degradome Products of the Matricellular Protein CCN1 as Modulators of Pathological Angiogenesis in the Retina

Choi

Lin

Shrier

et al. 2013

Journal of Biological Chemistry

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“…Immunohistochemical analyses of retinal tissue and protein analyses by western imunoblotting were performed as previously described (Chintala et al, 2012). For further details, see the supplementary material methods.…”

Section: Immunofluorescence and Immunoblottingmentioning

confidence: 99%

“…Quantitative analysis of mRNAs by qPCR was performed using TaqMan technology on ABI 7000 sequence detection system (Applied Biosystems) as previously described (Chintala et al, 2012). The primers used are further described in the supplementary material methods.…”

Section: Rna Isolation and Quantitative Analysis Of Mrnamentioning

confidence: 99%

The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling

et al. 2015

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Physiological angiogenesis depends on the highly coordinated actions of multiple angiogenic regulators. CCN1 is a secreted cysteine-rich and integrin-binding matricellular protein required for proper cardiovascular development. However, our understanding of the cellular origins and activities of this molecule is incomplete. Here, we show that CCN1 is predominantly expressed in angiogenic endothelial cells (ECs) at the leading front of actively growing vessels in the mouse retina. Endothelial deletion of CCN1 in mice using a Cre-Lox system is associated with EC hyperplasia, loss of pericyte coverage and formation of dense retinal vascular networks lacking the normal hierarchical arrangement of arterioles, capillaries and venules.

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“…In mice subjected to OIR, the CCN2 gene was overexpressed in neovascular areas and CCN2 protein localized within neovascular tufts (Chintala et al 2012). Unsurprisingly, silencing of CCN2 reduced neovascularization in the mouse OIR model.…”

Section: Ccn1 and Ccn2 In Retinopathy Of Prematuritymentioning

confidence: 99%

“…CCN2 expression coincides with the formation of primary, intermediary and deep capillary plexuses (Chintala et al 2012). When the retinal vasculature is completely established, the expression of CCN2 decline but maintains relatively high basal levels in the adult vasculature.…”

Section: Requirement Of Ccn1 and Ccn2 In Developmental Retinal Angiogmentioning

confidence: 99%

Cysteine‐rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy

Yan

Chaqour

2013

Journal of Cell Communication and Signaling

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The vasculature forms a highly branched network investing every organ of vertebrate organisms. The retinal circulation, in particular, is supported by a central retinal artery branching into superficial arteries, which dive into the retina to form a dense network of capillaries in the deeper retinal layers. The function of the retina is highly dependent on the integrity and proper functioning of its vascular network and numerous ocular diseases including diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity are caused by vascular abnormalities culminating in total and sometimes irreversible loss of vision. CCN1 and CCN2 are inducible extracellular matrix (ECM) proteins which play a major role in normal and aberrant formation of blood vessels as their expression is associated with developmental and pathological angiogenesis. Both CCN1 and CCN2 achieve disparate cell-type and context-dependent activities through modulation of the angiogenic and synthetic phenotype of vascular and mesenchymal cells respectively. At the molecular level, CCN1 and CCN2 may control capillary growth and vascular cell differentiation by altering the composition or function of the constitutive ECM proteins, potentiating or interfering with the activity of various ligands and/or their receptors, physically interfering with the ECM-cell surface interconnections, and/or reprogramming gene expression driving cells toward new phenotypes. As such, these proteins emerged as important prognostic markers and potential therapeutic targets in neovascular and fibrovascular diseases of the eye. The purpose of this review is to highlight our current knowledge and understanding of the most recent data linking CCN1 and CCN2 signaling to ocular neovascularization bolstering the potential value of targeting these proteins in a therapeutic context.

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Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

Cited by 44 publications

References 67 publications

Degradome Products of the Matricellular Protein CCN1 as Modulators of Pathological Angiogenesis in the Retina

Degradome Products of the Matricellular Protein CCN1 as Modulators of Pathological Angiogenesis in the Retina

The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling

Cysteine‐rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy

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