In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive. This study adopted three states of collagen I existing in ECM remodeling: molecular collagen, fibrillar collagen and gelatin to see what are characteristics in the effects on two cell lines of mesenchymal origin, murine 3T3-L1 embryonic fibroblast and murine C2C12 myoblasts. The results showed that all three forms of collagen I were capable of inducing these two cells to differentiate into myofibroblasts characterized by increased expression of alpha-smooth muscle actin (α-SMA) mRNA. The expression of α-SMA is positively regulated by TGF-β1. Nuclear translocation of Yes-associated protein (YAP) is involved in this process. Focal adhesion kinase (FAK) is activated in the cells cultured on molecular collagen-coated plates, contributing to YAP activation. On the other hand, in the cells cultured on fibrillar collagen gel or gelatin-coated plates, oxidative stress but not FAK induce YAP activation. In conclusion, the three physicochemically distinct forms of col I induce the differentiation of mesenchymal cells into myofibroblasts through different pathways.

在器官纤维化中，机械应力和转化生长因子β-1（TGF-β1）促进从间充质细胞分化为成肌纤维细胞，导致细胞外基质（ECM）重塑或ECM成分主动合成，沉积或降解。ECM的主要成分是I型胶原蛋白（col I）三重螺旋分子组装成原纤维或变性为明胶，而没有三重螺旋性。然而，ECM组件在重塑中的变化是否对间充质细胞分化产生影响尚不清楚。这项研究采用了存在于ECM重塑中的三种胶原蛋白I状态：分子胶原蛋白，纤维状胶原蛋白和明胶，以观察对间充质来源的两种细胞系，鼠类3T3-L1胚胎成纤维细胞和鼠类C2C12成肌细胞的影响特征。结果表明，所有三种形式的胶原蛋白I都能够诱导这两种细胞分化为成纤维细胞，其特征在于α平滑肌肌动蛋白（α-SMA）mRNA的表达增加。TGF-β1正调控α-SMA的表达。是相关蛋白（YAP）的核易位参与此过程。粘着斑激酶（FAK）在分子胶原包被的平板上培养的细胞中被激活，从而促进了YAP的激活。另一方面，在原纤维胶原蛋白凝胶或明胶包被的平板上培养的细胞中，氧化应激而不是FAK诱导YAP活化。总之，col I的三种物理化学不同形式可通过不同途径诱导间充质细胞分化为成肌纤维细胞。