Artificial extracellular matrix composed of collagen I and highly sulfated hyaluronan interferes with TGF beta(1) signaling and prevents TGF beta(1)-induced myofibroblast differentiation

作者：van der Smissen Anja^*; Samsonov Sergey; Hintze Vera; Scharnweber Dieter; Moeller Stephanie; Schnabelrauch Matthias; Pisabarro M Teresa; Anderegg Ulf

来源：Acta Biomaterialia, 2013, 9(8): 7775-7786.

DOI：10.1016/j.actbio.2013.04.023

• Wound healing
• Myofibroblast
• Transforming growth factor beta 1
• Collagen I
• Sulfated hyaluronan

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 beta 1 (TGF beta 1). The synthesis of alpha-smooth muscle actin (alpha SMA), 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 beta 1 in the presence of aECM and finally made interaction studies of soluble HA or hsHA with TGF beta 1. Artificial ECM composed of coll and hsHA prevents TGF beta 1-stimulated alpha SMA, collagen and ED-A FN expression. Our data suggest an impaired TGF beta 1 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 beta-receptor I binding site by hsHA. Possibly, HA sulfation has a strong impact on TGF beta 1-driven differentiation of dFb and thus could be used to modulate the properties of biomaterials.

• 出版日期2013-8