Artificial extracellular matrix composed of collagen I and highly sulfated hyaluronan interferes with TGF¦Â₁ signaling and prevents TGF¦Â₁-induced myofibroblast differentiation

详细信息    查看全文

• 作者：Anja van der Smissen ; Sergey Samsonov ; Vera Hintze ; Dieter Scharnweber ; Stephanie Moeller ; Matthias Schnabelrauch ; M. Teresa Pisabarro ; Ulf Anderegg
• 关键词：Wound healing ; Myofibroblast ; Transforming growth factor ¦Â1 ; Collagen I ; Sulfated hyaluronan
• 刊名：Acta Biomaterialia
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：9
• 期：8
• 页码：7775-7786
• 全文大小：3139 K

文摘

Sulfated glycosaminoglycans are promising components for functional biomaterials since sulfate groups modulate the binding of growth factors and thereby influence wound healing. Here, we have investigated the influence of an artificial extracellular matrix (aECM) consisting of collagen I (coll) and hyaluronan (HA) or highly sulfated HA (hsHA) on dermal fibroblasts (dFb) with respect to their differentiation into myofibroblasts (MFb). Fibroblasts were cultured on aECM in the presence of aECM-adsorbed or soluble transforming growth factor ¦Â1 (TGF¦Â1). The synthesis of ¦Á-smooth muscle actin (¦ÁSMA), collagen and the ED-A splice variant of fibronectin (ED-A FN) were analyzed at the mRNA and protein levels. Furthermore, we investigated the bioactivity and signal transduction of TGF¦Â1 in the presence of aECM and finally made interaction studies of soluble HA or hsHA with TGF¦Â1. Artificial ECM composed of coll and hsHA prevents TGF¦Â1-stimulated ¦ÁSMA, collagen and ED-A FN expression. Our data suggest an impaired TGF¦Â1 bioactivity and downstream signaling in the presence of aECM containing hsHA, shown by massively reduced Smad2/3 translocation to the nucleus. These data are explained by in silico docking experiments demonstrating the occupation of the TGF¦Â-receptor I binding site by hsHA. Possibly, HA sulfation has a strong impact on TGF¦Â1-driven differentiation of dFb and thus could be used to modulate the properties of biomaterials.