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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >Chemically modified dextrans modulate expression of collagen phenotype by cultured smooth muscle cells in relation to the degree of carboxymethyl, benzylamide, and sulfation substitutions.
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Chemically modified dextrans modulate expression of collagen phenotype by cultured smooth muscle cells in relation to the degree of carboxymethyl, benzylamide, and sulfation substitutions.

机译:化学修饰的右旋糖酐可以调节培养的平滑肌细胞的胶原表型表达,与羧甲基,苄基酰胺和硫酸盐取代的程度有关。

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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.
机译:我们开发了与衍生自葡聚糖的多糖相对应的再生剂(RGTA),该再生剂包含不同取代度的羧甲基(CM),羧甲基硫酸(CMS),羧甲基苄酰胺(CMB)或羧甲基苄酰胺硫酸(CMBS)基团。这些化合物模仿了肝素对平滑肌细胞(SMC)增殖的某些作用,并促进了体内组织重塑。我们证明只有含有CM和硫酸盐基团的RGTA会降低SMC增殖,并与硫酸化水平增加相关。苄酰胺的存在增强了这种作用。不依赖于这种对细胞增殖的活性(即融合后的细胞),RGTA调节SMCs的胶原生物合成。一方面,与CMS RGTA相比,CMBS在mRNA稳态和蛋白质产生水平上诱导了胶原III合成的减少。另一方面,CMS比CMBS RGTA更大程度地增加了胶原V mRNA和蛋白质的产生。此外,仅含苄基酰胺的RGTA会增加胶原蛋白I和III在细胞层中的积累。总之,RGTA生物活性要求存在CM功能,随着硫酸化程度的增加而增加,并随苄基酰胺取代而变化。通过差异机制调节细胞增殖和胶原生物合成的RGTA可能代表了潜在的抗纤维化剂。

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