Derivatized dextrans modulate collagen synthesis in aortic smooth muscle cells

We developed regenerating agents (RGTAs) corresponding to polysaccharides derived from dextran and containing defined amounts of carboxymethyl (CM), carboxymethyl sulfate (CMS), carboxymethyl benzylamide (CMB), or carboxymethyl benzylamide sulfate (CMBS) groups with varying degrees of substitution. These compounds mimicked some effects of heparin on smooth muscle cell (SMC) proliferation and promoted in vivo tissue remodeling. We demonstrated that only RGTAs containing both CM and sulfate groups decreased SMC proliferation, in correlation with increased sulfation level. This effect was amplified by the presence of benzylamide. Independent of this activity on cell proliferation (i.e., with postconfluent cells), RGTAs modulated collagen biosynthesis by SMCs. On the one hand, CMBS more than CMS RGTAs induced a decrease of collagen III synthesis at the level of mRNA steady state and protein production. On the other hand, CMS to a greater extent than CMBS RGTAs increased both collagen V mRNA and protein production. In addition, only benzylamide-containing RGTAs increased accumulation of collagen I and III in the cell layer. In conclusion, RGTA bioactivities required the presence of CM functions, increased with the sulfation level, and varied with benzylamide substitution. RGTAs that modulate cell proliferation and collagen biosynthesis by differential mechanisms may represent potential antifibrotic agents.

“…15,16 Cell proliferation studies SMCs were passaged serially with 10% FCS. In all experiments SMCs were used at the third passage.…”

Section: Cell Culturementioning

confidence: 99%

Section: Rna Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chemically modified dextrans modulate expression of collagen phenotype by cultured smooth muscle cells in relation to the degree of carboxymethyl, benzylamide, and sulfation substitutions

Mestries

Borchiellini

Barbaud

et al. 1998

Collagen synthesis by vascular smooth muscle cells in the presence of antiproliferative polysaccharides

Logeart

Letourneur

Jozefonvicz

et al. 1996

Self Cite

Production of various components of the extracellular matrix (ECM) modulates biological functions of the vascular tissue. This process is generally amplified in pathologic states as atherosclerosis. Atheroma originates from smooth muscle cells (SMC) which have migrated and proliferated in the vascular intima. In this study we investigated protein synthesis, collagen synthesis, and types I, III, and V collagen distribution by SMC in the presence of three families of watersoluble polysaccharides, heparin, fucans, and derivatized dextrans. We observed that fucan and derivatized dextran were able, as was heparin, to inhibit rat aortic SMC growth in culture. We then analyzed collagen modulation by measuring the incorporation of the radiolabeled precursor (3H)-proline into vascular SMC. Our results showed uncoupling of the antiproliferative capacity with collagen biosynthesis. However, fucan, the most antiproliferative polysaccharide, was also the most active in inhibiting protein and collagen synthesis. In addition, compounds that decreased total collagen synthesis preferentially increased the proportion of cell-associated collagen. Interestingly, only the antiproliferative polysaccharides inhibited significantly type V collagen biosynthesis. These new biomaterials appear to be valuable tools to study and control extracellular-matrix interactions with cells from the vascular walls.

Antiproliferative polysaccharides modulate distribution and phenotypic expression of collagens by gingival fibroblasts

Senni

Borchiellini

Duchesnay

et al. 1998

Self Cite

Gingival fibroblasts are particularly involved in the physiologic maintenance and repair of periodontium. During these processes, cell proliferation and synthesis of a collagen-rich gingival matrix should be controlled. A dextran derivative, namely, carboxy methyl dextran benzylamide sulfonate (CMDBS), considered to be a functional analog of heparin, was previously described to regulate proliferation of different types of cells and independently to modulate the expression of collagen biosynthesis. In this report, we demonstrate that CMDBS and heparin inhibited gingival fibroblast proliferation. We then analyzed collagen biosynthesis by measuring the incorporation of the radiolabeled [3H]proline precursor into collagen by postconfluent gingival fibroblasts. Our results showed CMDBS did not alter total collagen synthesis; it induced the preferential accumulation of newly synthesized collagen into the pericellular matrix; and it decreased the expression of type III collagen, particularly in the cell layer. Taken together, our results suggest that by inhibiting cell proliferation, CMDBS could induce the synthesis of an extracellular collagenous matrix which forms a network between gingival fibroblasts.