Effect of heparin on the production of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human dermal fibroblasts

Gogly, Bruno; Dridi, M; Hornebeck, William; Bonnefoix, Mireille; Godeau, Gaston; Pellat, B.

doi:10.1006/cbir.1998.0334

Cited by 16 publications

(8 citation statements)

References 24 publications

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“…Heparin has been reported to decrease phorbolesterstimulated MMP-9 expression while having no effect on MMP-2 or TIMP-1 (22,23). Thus, it is possible that we may have underestimated the effect of FFA on MMP-9.…”

Section: Discussionmentioning

confidence: 93%

In Vivo Effects of Insulin and Free Fatty Acids on Matrix Metalloproteinases in Rat Aorta

et al. 2008

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OBJECTIVE-Obesity is associated with insulin resistance, hyperinsulinemia, elevated plasma free fatty acid (FFA), and increased risk for atherosclerotic vascular disease (ASVD). A part of this increased risk may be due to enhanced activation of matrix metalloproteinases (MMPs). Here, we have examined the effects of physiologically elevated levels of insulin and FFA on three MMPs and their inhibitors (tissue inhibitors of MMP [TIMPs]) in aortic tissue of male rats during euglycemic-hyperinsulinemic clamping.RESEARCH DESIGN AND METHODS-Four-hour euglycemic-hyperinsulinemic clamps with infusion of saline/glycerol, lipid/heparin, or insulin with or without lipid/heparin were performed in alert unrestrained male rats.RESULTS-Hyperinsulinemia increased MMP-2 (ϳ6-fold), MMP-9 (ϳ13-fold), membrane type 1-MMP (MT1-MMP; ϳ8-fold) (all Western blots), and gelatinolytic activity (zymography) of MMP-2 (2-fold), while not affecting TIMP-1 and TIMP-2. Insulin increased IRS-1-associated PI 3-kinase (PI3K), extracellular signal-regulated kinases 1/2 (ERK1/2), and c-jun NH 2 -terminal kinase (JNK) (by Western blots with phospho-specific antibodies). FFA augmented the insulin-mediated increases in MMP-2 (from ϳ6-to ϳ11-fold), MMP-9 (from ϳ3-to ϳ23-fold), MT1-MMP (from ϳ8-to ϳ20-fold), MMP-2 gelatinolytic activity (from 2-to 3-fold), and JNK and p38 mitogen-activated protein kinase (MAPK) activities but decreased insulin-mediated activation of PI3K and ERK1/2. Raising FFA without raising insulin affected neither MMPs nor TIMPs.CONCLUSIONS-FFA augmented insulin stimulation of the MMP/TIMP balance of three proatherogenic MMPs and increased activities of two MAPKs (JNK and p38 MAPK), both of which are known to stimulate the production of proinflammatory cytokines. This may, over time, increase degradation of extracellular matrix and together with inflammatory changes promote development of ASVD. Diabetes 57:476-483, 2008 M any obese people are insulin resistant (1,2). Insulin resistance, on the other hand, is one of the most important risk factors for the development and progression of atherosclerotic vascular disease (ASVD) (3,4). The relationship between insulin resistance and ASVD, however, is complex. On one hand, insulin resistance is associated with several established risk factors for ASVD such as type 2 diabetes, hypertension, atherogenic dyslipidemia, and abnormalities of blood coagulation and fibrinolysis (5). On the other hand, these associations cannot completely explain the obesity/insulin resistance-related ASVD risk, suggesting that there may be other, as yet unidentified, ways in which insulin resistance increases this risk (6). Indeed, there are reasons to believe that insulin resistance may increase ASVD by promoting matrix metalloproteinase (MMP) activity. MMPs are enzymes with proteolytic activity against connective tissue proteins such as collagen, proteoglycans, and elastin and there is accumulating evidence suggesting that they play a key role in the development of atherosclerotic lesions (rev. in 7). For instanc...

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Section: Discussionmentioning

confidence: 93%

In Vivo Effects of Insulin and Free Fatty Acids on Matrix Metalloproteinases in Rat Aorta

et al. 2008

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“…It has been reported that both heparin and chondroitin sulfate inhibit the overexpression of MMP-1 and MMP-3 by IL-1 ® in mesenchymal cells, such as mesangial cells [39], gingival fibroblasts [17], synovial fibroblasts or chondrocytes [40,41]. Thus, mechanisms explaining inhibition of IL-1 ® signaling by sulfated GAGs may involve the inhibition of protein kinase C (PKC)-dependent pathways [16] or alteration in intracellular trafficking mediated by calcium [42].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies demonstrated that both heparin and chondroitin-sulfate directly inhibit serine-proteinase activities [14,15] and modulate matrix metalloproteinase syntheses in cell culture [16,17]. Furthermore, heparan-sulfates of endothelial cell surfaces are key players in leukocyte homing and rolling and show good affinities for chemokines and selectins [18,19].…”

Section: Introductionmentioning

confidence: 99%

Unusual Glycosaminoglycans from a Deep Sea Hydrothermal Bacterium Improve Fibrillar Collagen Structuring and Fibroblast Activities in Engineered Connective Tissues

et al. 2013

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Biopolymers produced by marine organisms can offer useful tools for regenerative medicine. Particularly, HE800 exopolysaccharide (HE800 EPS) secreted by a deep-sea hydrothermal bacterium displays an interesting glycosaminoglycan-like feature resembling hyaluronan. Previous studies demonstrated its effectiveness to enhance in vivo bone regeneration and to support osteoblastic cell metabolism in culture. Thus, in order to assess the usefulness of this high-molecular weight polymer in tissue engineering and tissue repair, in vitro reconstructed connective tissues containing HE800 EPS were performed. We showed that this polysaccharide promotes both collagen structuring and extracellular matrix settle by dermal fibroblasts. Furthermore, from the native HE800 EPS, a low-molecular weight sulfated derivative (HE800 DROS) displaying chemical analogy with heparan-sulfate, was designed. Thus, it was demonstrated that HE800 DROS mimics some properties of heparan-sulfate, such as promotion of fibroblast proliferation and inhibition of matrix metalloproteinase (MMP) secretion. Therefore, we suggest that the HE800EPS family can be considered as an innovative biotechnological source of glycosaminoglycan-like compounds useful to design biomaterials and drugs for tissue engineering and repair.

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“…Their ability to structure matrix macromolecules has been described on collagens as well as on matrix glycoproteins or elastic fibers [15–17]. Other studies demonstrated that heparin and chondroitin-sulfate directly inhibit serine-proteinase activity and modulate matrix metalloproteinase activity in cell culture [18,19]. Due to specific interactions with chemokines and selectins, heparan-sulfates found on endothelial cell surface are also major actors in leukocyte rolling and chemo-attraction [20,21].…”

Section: Glycosaminoglycans: Structural Features Biological Propementioning

confidence: 99%

Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering

Senni¹,

et al. 2011

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The therapeutic potential of natural bioactive compounds such as polysaccharides, especially glycosaminoglycans, is now well documented, and this activity combined with natural biodiversity will allow the development of a new generation of therapeutics. Advances in our understanding of the biosynthesis, structure and function of complex glycans from mammalian origin have shown the crucial role of this class of molecules to modulate disease processes and the importance of a deeper knowledge of structure-activity relationships. Marine environment offers a tremendous biodiversity and original polysaccharides have been discovered presenting a great chemical diversity that is largely species specific. The study of the biological properties of the polysaccharides from marine eukaryotes and marine prokaryotes revealed that the polysaccharides from the marine environment could provide a valid alternative to traditional polysaccharides such as glycosaminoglycans. Marine polysaccharides present a real potential for natural product drug discovery and for the delivery of new marine derived products for therapeutic applications.

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Effect of heparin on the production of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human dermal fibroblasts

Cited by 16 publications

References 24 publications

In Vivo Effects of Insulin and Free Fatty Acids on Matrix Metalloproteinases in Rat Aorta

In Vivo Effects of Insulin and Free Fatty Acids on Matrix Metalloproteinases in Rat Aorta

Unusual Glycosaminoglycans from a Deep Sea Hydrothermal Bacterium Improve Fibrillar Collagen Structuring and Fibroblast Activities in Engineered Connective Tissues

Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering

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