Spurlin Tighe A, Bhadriraju Kiran, Chung Koo-Hyun, Tona Alessandro, Plant Anne L
Biochemical Science Division, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, USA.
Biomaterials. 2009 Oct;30(29):5486-96. doi: 10.1016/j.biomaterials.2009.07.014. Epub 2009 Jul 28.
The enzyme tissue transglutaminase 2 (TG2) appears to play an important role in several physiological processes such as wound healing, the progression of cancer and of vascular disease. Additionally, TG2 has been proposed as a means of stabilizing collagen extracellular matrix (ECM) scaffolds for tissue engineering applications. In this report, we examined the effect of TG2 treatment on the mechanical properties of the ECM, and associated cell responses. Using a model ECM of fibrillar collagen, we quantitatively examined vascular smooth muscle cell (vSMC) response to untreated, or TG2 treated collagen. We show that cells respond to TG2 treated collagen with increased spreading, an increase in contractile response as indicated by elevated F-actin polymerization and myosin light chain phosphorylation, and increased proliferation, without apparent changes in integrin specificity or matrix topography. Comparative atomic force microscopy loading studies indicate that TG2 treated fibrils are 3 times more resistant to shearing force from an AFM tip than untreated fibrils. The data suggest that TG2 treatment of collagen increases matrix mechanical stiffness, which apparently alters the contractile and proliferative response of vSMC.
组织转谷氨酰胺酶2（TG2）似乎在多种生理过程中发挥重要作用，如伤口愈合、癌症进展和血管疾病发展。此外，TG2已被提议作为一种稳定用于组织工程应用的胶原蛋白细胞外基质（ECM）支架的方法。在本报告中，我们研究了TG2处理对ECM力学性能及相关细胞反应的影响。使用纤维状胶原蛋白的模型ECM，我们定量研究了血管平滑肌细胞（vSMC）对未处理或TG2处理的胶原蛋白的反应。我们发现，细胞对TG2处理的胶原蛋白的反应是铺展增加、收缩反应增强（表现为F-肌动蛋白聚合和肌球蛋白轻链磷酸化升高）以及增殖增加，而整合素特异性或基质拓扑结构无明显变化。比较原子力显微镜加载研究表明，TG2处理的纤维对原子力显微镜探针剪切力的抵抗力是未处理纤维的3倍。数据表明，TG2处理胶原蛋白会增加基质机械硬度，这显然改变了vSMC的收缩和增殖反应。
