Matrix Metalloproteinases Cleave Connective Tissue Growth Factor and Reactivate Angiogenic Activity of Vascular Endothelial Growth Factor 165

Hashimoto, Gakuji; Inoki, Isao; Fujii, Yutaka; Aoki, Takanori; Ikeda, Eiji; Okada, Yasunori

doi:10.1074/jbc.m201674200

Cited by 323 publications

(310 citation statements)

References 53 publications

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“…The peptides identified and the molecular weight observed indicate CTGF processing at the MMP-sensitive linker region between von Willebrand factor C and TSP-1 repeat domains (45). Interestingly, MMP-mediated cleavage of CTGF at this site is a newly described mechanism for releasing CTGFbound vascular endothelial growth factor (46).…”

Section: Discussionmentioning

confidence: 91%

Proteomic characterization of mouse cartilage degradation in vitro

Wilson¹,

Belluoccio²,

Little³

et al. 2008

Arthritis & Rheumatism

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Objective.To develop proteomics to analyze mouse cartilage degradation and correlate transcriptional and translational responses to catabolic stimuli.Methods. Proteomic techniques were used to analyze catabolism in mouse femoral head cartilage. Using specific methods to prepare cartilage extracts and conditioned media for 2-dimensional polyacrylamide gel electrophoresis and subsequent tandem mass spectrometry, we identified novel proteins and fragments released into the media of control, interleukin-1␣ (IL-1␣)-treated, and all-trans-retinoic acid (RetA)-treated explants. Fluorescence 2-dimensional difference gel electrophoresis was used to quantify protein expression changes. We also measured changes in messenger RNA (mRNA) expression to distinguish transcriptional and posttranslational regulation of released proteins.Results. Differentially abundant proteins in the media of control and treated explants included fragments of thrombospondin 1 and connective tissue growth factor. IL-1␣ stimulated release of the cartilage degeneration marker matrix metalloproteinase 3, as well as proteins with uncharacterized roles in cartilage pathology, such as neutrophil gelatinase-associated lipocalin. RetA stimulated release of the extracellular matrix proteins cartilage oligomeric matrix protein, link protein, and matrilin-3 into the media, which was accompanied by a dramatic reduction in the corresponding mRNA transcript levels. Gelsolin, which has been implicated in cytoskeletal reorganization in arthritis synovial fibroblasts but has not been previously associated with cartilage pathology, was regulated by IL-1␣ and RetA.Conclusion. In this first analysis of mouse cartilage degradation and protein release using proteomics, we identified proteins and fragments, some of which represent novel candidate biomarkers for cartilage degradation. Applying these proteomic techniques to wild-type and genetically modified mouse cartilage will provide insights into the mechanisms of cartilage degeneration.

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Section: Discussionmentioning

confidence: 91%

Proteomic characterization of mouse cartilage degradation in vitro

Wilson¹,

Belluoccio²,

Little³

et al. 2008

Arthritis & Rheumatism

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show abstract

“…expressions being enhanced by VEGF (28,29). MMP-2 and membrane type-1-MMP (MT-1-MMP) are enzymes with roles in angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol Inhibits Vascular Endothelial Growth Factor-A– Induced Migration of Human Umbilical Vein Endothelial Cells

et al. 2008

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“…Our data suggest a regulation of VEGF activity by CTGF and MMP-7 in human cells and tissues. Human MMP-7 and other MMPs do not cleave the predominant isoform of VEGF (VEGF 165 ) in vitro (Keyt et al, 1996;Hashimoto et al, 2002), which leads to selective degradation of CTGF and the release of VEGF activity . In contrast, MMP-7 and other MMPs modulate bioactivity of the corresponding isoform of mouse VEGF through intramolecular cleavage (Lee et al, 2005).…”

Section: Mmp-7 Activates Latent Vegf From Fibroblasts T-k Ito Et Almentioning

confidence: 99%

The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells

et al. 2007

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Matrix Metalloproteinases Cleave Connective Tissue Growth Factor and Reactivate Angiogenic Activity of Vascular Endothelial Growth Factor 165

Cited by 323 publications

References 53 publications

Proteomic characterization of mouse cartilage degradation in vitro

Proteomic characterization of mouse cartilage degradation in vitro

Phosphatidylinositol Inhibits Vascular Endothelial Growth Factor-A– Induced Migration of Human Umbilical Vein Endothelial Cells

The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells

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