Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices.
Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices.
复制标题
DOI：
10.1016/j.carpath.2010.10.001
复制
发表时间：
2011-11
影响因子：
3.7
通讯作者：
Stegemann, Jan P.
中科院分区：
文献类型：
--
作者：
Galie, Peter A.;Westfall, Margaret V.;Stegemann, Jan P.
成纤维细胞-肌成纤维细胞转化是心肌缺血后心肌纤维化和瘢痕形成过程中的重要事件。本研究的目的是更好地了解环境因素对这种转变的贡献，并确定肌成纤维细胞是否对周围环境提供同样重要的反馈。通过定量RT-PCR检测一组心肌成纤维细胞表型标记物的信息水平，评估基质硬度和血清浓度对肌成纤维细胞转化的影响。细胞介导的凝胶压实测量了环境因素对心脏成纤维细胞收缩能力的影响。免疫组织化学检测α-SMA的表达和细胞形态，静态和动态压缩试验评价细胞反应对细胞接种的胶原水凝胶力学性能的影响。血清含量的降低和基质硬度的增加都有助于肌成纤维细胞的转变，表现为凝胶的收缩致密，COL3α1和α-SMA的信息水平增加，以及较少的星状形态。然而，血清和基质硬度的影响不是相加的。力学测试表明，随着时间的推移，细胞种子凝胶的粘弹性变得较小，而血清含量的减少也增加了凝胶的初始弹性。结果表明，降低血清和增加基质硬度可促进心肌成纤维细胞的表型。这一转变既增强了基质刚性，也促进了基质刚性，表明存在正反馈，这可能有助于心脏纤维化的发病机制。较低的血清含量和较高的基质硬度加速了种植在胶原水凝胶中的心脏成纤维细胞向肌成纤维细胞表型的转变，尽管它们的影响不是相加的。降低的血清也影响了水凝胶的机械性能，这表明肌成纤维细胞的转变既增加了又被基质僵硬加速。这种正反馈可能参与了心脏纤维化的发病机制。
The fibroblast-myofibroblast transition is an important event in the development of cardiac fibrosis and scar formation initiated after myocardial ischemia. The goals of the present study were to better understand the contribution of environmental factors to this transition and determine whether myofibroblasts provide equally important feedback to the surrounding environment. The influence of matrix stiffness and serum concentration on the myofibroblast transition was assessed by measuring message levels of a panel of cardiac fibroblast phenotype markers using quantitative rtPCR. Cell-mediated gel compaction measured the influence of environmental factors on cardiac fibroblast contractility. Immunohistochemistry characterized α-SMA expression and cell morphology, while static and dynamic compression testing evaluated the effect of the cell response on the mechanical properties of the cell-seeded collagen hydrogels. Both reduced serum content and increased matrix stiffness contributed to the myofibroblast transition, as indicated by contractile compaction of the gels, increased message levels of col3α1 and α-SMA, and a less stellate morphology. However, the effects of serum and matrix stiffness were not additive. Mechanical testing indicated the cell-seeded gels became less viscoelastic with time, and that reduced serum content also increased the initial elastic properties of the gel. The results suggest that reduced serum and increased matrix stiffness promote the myofibroblast phenotype in the myocardium. This transition both enhances and is promoted by matrix stiffness, indicating the presence of positive feedback that may contribute to the pathogenesis of cardiac fibrosis. Lower serum content and increased matrix stiffness accelerated the transition of cardiac fibroblasts seeded in collagen hydrogels to a myofibroblast phenotype, though their effects were not additive. Reduced serum also affected mechanical properties of the hydrogels, suggesting that the myofibroblast transition both augments and is accelerated by matrix stiffness. This positive feedback may contribute to cardiac fibrosis pathogenesis.
登录
查看更多内容
DOI：
10.1089/ten.teb.2009.0270
发表时间：
2009-09
期刊：
Tissue engineering. Part B, Reviews
影响因子：
--
作者：
Lund AW;Yener B;Stegemann JP;Plopper GE
通讯作者：
Plopper GE
影响因子：
4.8
作者：
Fringer, J;Grinnell, F
通讯作者：
Grinnell, F
DOI：
10.1152/ajpheart.00369.2009
发表时间：
2009-10-01
影响因子：
4.8
作者：
Shi, Zhong-Dong;Ji, Xin-Ying;Tarbell, John M.
通讯作者：
Tarbell, John M.
DOI：
10.1358/mf.2003.25.2.723680
发表时间：
2003-03-01
影响因子：
--
作者：
Lijnen, P;Petrov, V;Fagard, R
通讯作者：
Fagard, R
影响因子：
5
作者：
Butt, RP;Bishop, JE
通讯作者：
Bishop, JE