Investigating the role of fibrinogen during BMP signaling

Abstract

Bone Morphogenetic Protein signaling plays crucial roles regulating cellular behaviors, tissue homeostasis and regeneration. Considering that many diseases are caused by BMP signaling failure, tight regulation of BMP signaling is important issue. Recently, the role of fibrinogen in BMP signaling has been investigated in neural stem cells. It was reported that during blood-brain barrier disruption, fibrinogen activates BMP signaling to induce cell fate decision toward astrogenesis in neural stem cells and progenitor cells by binding to integrin receptor. However, little is known about the regulating mechanism of fibrinogen in BMP signal transduction other than neuronal cell types. To investigate signaling diversity of fibrinogen in BMP signaling, I confirmed activation of downstream targets in fibrinogen-induced BMP signaling in endothelial cells and fibroblasts. Then I examined that fibrinogen-induced BMP signaling is not because of fibrinogen-induced viscosity. Fibrinogen required BMP type I receptors to activate BMP signaling in a redundant manner ALK2 and ALK3. Plus, simultaneous treatment of BMP ligands and fibrinogen showed different ability to activate BMP signaling. Finally, I examined that fibrinogen transduces BMP signal through dynamin-independent pathway. These data collectively demonstrate that fibrinogen can act as a novel BMP signaling agent which activates BMP signaling pathway in other cell types besides neuronal cells. Further analysis of fibrinogen-mediated BMP signaling will elucidate complex nature in regulation of BMP signaling.