Heparin-binding fragments of fibronectin are potent inhibitors of endothelial cell growth: structure-function correlations

Homandberg, Gene A.; Kramer-Bjerke, J.; Grant, Debra; Christianson, Gregory J.; Eisenstein, Reuben

doi:10.1016/0167-4838(86)90102-0

Cited by 81 publications

(47 citation statements)

References 40 publications

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“…Fibronectin fragments have been shown to possess different biologic activities like the inhibition of Schwann cells proliferation or the inhibition of endothelial cells growth. 36,37 It is also interesting to note that perlecan DV and fibronectin have been shown to modulate angiogenesis via the same receptor, a5b1 integrin, suggesting its relative importance to brain angiogenesis. 16,22 Link between Integrin and Angiogenesis Perlecan DV binding to a5b1 integrin can induce VEGF release, 16 and whereas a5b1 integrin and fibronectin are both poorly expressed in quiescent endothelium, they are strongly expressed in proliferating vessels.…”

Section: Discussionmentioning

confidence: 99%

Juvenile Traumatic Brain Injury Induces Long-Term Perivascular Matrix Changes Alongside Amyloid-Beta Accumulation

Jullienne

Roberts

Pop

et al. 2014

J Cereb Blood Flow Metab

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In our juvenile traumatic brain injury (jTBI) model, emergence of cognitive dysfunctions was observed up to 6 months after trauma. Here we hypothesize that early brain injury induces changes in the neurovascular unit (NVU) that would be associated with amyloid-beta (Ab) accumulation. We investigated NVU changes for up to 6 months in a rat jTBI model, with a focus on the efflux protein P-glycoprotein (P-gp) and on the basement membrane proteins perlecan and fibronectin, all known to be involved in Ab clearance. Rodent-Ab staining is present and increased after jTBI around cerebral blood microvessels, and the diameter of those is decreased by 25% and 34% at 2 and 6 months, respectively, without significant angiogenesis. P-glycoprotein staining in endothelium is decreased by 22% and parallels an increase of perlecan and fibronectin staining around cerebral blood vessels. Altogether, these results strongly suggest that the emergence of long-term behavioral dysfunctions observed in rodent jTBI may be related to endothelial remodeling at the blood-brain barrier alongside vascular dysfunction and altered Ab trafficking. This study shows that it is important to consider jTBI as a vascular disorder with long-term consequences on cognitive functions.

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Section: Discussionmentioning

confidence: 99%

Juvenile Traumatic Brain Injury Induces Long-Term Perivascular Matrix Changes Alongside Amyloid-Beta Accumulation

Jullienne

Roberts

Pop

et al. 2014

J Cereb Blood Flow Metab

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“…6A-C). Certain fibronectin fragments can promote inflammation (Barilla and Carsons, 2000;Norris et al, 1982), whereas other fibronectin fragments are known to regulate cell migration, growth and survival (Clark et al, 1988;Dai et al, 2005;Homandberg et al, 1985). Therefore, tight regulation of ECM fibronectin degradation and endocytosis provides a mechanism for limiting the accumulation of bioactive matrix fragments.…”

Section: Mt1-mmp Regulates Fibronectin Turnover 4045mentioning

confidence: 99%

MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin

Shi

Sottile

2011

Journal of Cell Science

111

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SummaryThe extracellular matrix (ECM) is dynamically remodeled by cells during development, normal tissue homeostasis and in a variety of disease processes. We previously showed that fibronectin is an important regulator of ECM remodeling. The deposition and/or polymerization of fibronectin into the ECM controls the deposition and stability of other ECM molecules. In addition, agents that inhibit fibronectin polymerization promote the turnover of fibronectin fibrils and enhance ECM fibronectin endocytosis and intracellular degradation. Endocytosis of ECM fibronectin is regulated by b1 integrins, including a5b1 integrin. We have examined the role of extracellular proteases in regulating ECM fibronectin turnover. Our data show that membrane type matrix metalloproteinase 1 (MT1-MMP; also known as MMP14) is a crucial regulator of fibronectin turnover. Cells lacking MT1-MMP show reduced turnover and endocytosis of ECM fibronectin. MT1-MMP regulates ECM fibronectin remodeling by promoting extracellular cleavage of fibronectin and by regulating a5b1-integrin endocytosis. Our data also show that fibronectin polymerization stabilizes fibronectin fibrils and inhibits ECM fibronectin endocytosis by inhibiting a5b1-integrin endocytosis. These data are the first to show that an ECM protein and its modifying enzyme can regulate integrin endocytosis. These data also show that integrin trafficking plays a major role in modulating ECM fibronectin remodeling. The dual dependence of ECM fibronectin turnover on extracellular proteolysis and endocytosis highlights the complex regulatory mechanisms that control ECM remodeling to ensure maintenance of proper tissue function.

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“…HS selectively increases cellular PGI/AMF binding at acid and not neutral pH identifying HS as a cellular receptor for PGI/AMF under acidic conditions. Although FN has two defined HS-binding sites (Homandberg et al, 1985), the presence of HS does not enhance PGI/AMF binding to FN fibrils and increases PGI/AMF binding to FN -/-cells. HS therefore mediates the FN-independent interaction of PGI/AMF with the cell under acidic conditions.…”

Section: Discussionmentioning

confidence: 88%

“…Acid-dependent sequestration of PGI/AMF cytokine activity by FN HS is implicated in ECM-mediated sequestration of multiple cytokines and has been shown to bind specifically to matricryptic sites in FN (Homandberg et al, 1985). To determine if HS is involved in the association of PGI/AMF with FN fibrils, NIH-3T3 cells were pretreated with Journal of Cell Science 118 (18) bPGI/AMF in complete medium (A-F) or with complete medium in the absence of bPGI/AMF (G-I) for 30 minutes at 37°C.…”

Section: Direct Interaction Of Pgi/amf With Fn At Acid But Not Neutramentioning

confidence: 99%

pH-specific sequestration of phosphoglucose isomerase/autocrine motility factor by fibronectin and heparan sulphate

Lagana

Goetz

Nathalie

et al. 2005

Journal of Cell Science

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Phosphoglucose isomerase (PGI) is a glycolytic enzyme that moonlights as a cytokine under the aliases autocrine motility factor (AMF), neuroleukin and maturation factor. The cytokine function of PGI/AMF targets multiple cell types however mechanisms that regulate and sequester this ubiquitous, circulating cytokine remain largely unidentified. PGI/AMF is shown here to exhibit fibronectin (FN)-dependent cell surface association at both neutral and acid pH. Direct PGI/AMF binding to FN and fluorescence resonance energy transfer (FRET) between PGI/AMF and FN were detected only at pH 5. At neutral pH, the interaction of PGI/AMF with FN is receptor-mediated requiring prior clathrin-dependent endocytosis. PGI/AMF and FN do not co-internalize and PGI/AMF undergoes a second round of endocytosis upon recycling to the plasma membrane indicating that recycling PGI/AMF receptor complexes associate with FN fibrils. Heparan sulphate does not affect cell association of PGI/AMF at neutral pH but enhances the FN-independent cell surface association of PGI/AMF at acid pH identifying two distinct mechanisms for PGI/AMF sequestration under acidic conditions. However, only PGI/AMF sequestration by FN at acid pH was able to stimulate cell motility upon pH neutralization identifying FN as a pH-dependent cytokine trap for PGI/AMF. The multiple ways of cellular association of PGI/AMF may represent acquired mechanisms to regulate and harness the cytokine function of PGI/AMF.

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Heparin-binding fragments of fibronectin are potent inhibitors of endothelial cell growth: structure-function correlations

Cited by 81 publications

References 40 publications

Juvenile Traumatic Brain Injury Induces Long-Term Perivascular Matrix Changes Alongside Amyloid-Beta Accumulation

Juvenile Traumatic Brain Injury Induces Long-Term Perivascular Matrix Changes Alongside Amyloid-Beta Accumulation

MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin

pH-specific sequestration of phosphoglucose isomerase/autocrine motility factor by fibronectin and heparan sulphate

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