The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin matrix.
Fibrinogen is a soluble protein produced by hepatocytes and secreted into plasma, where it functions in hemostasis. During inflammation, the hepatic synthesis of fibrinogen is induced 2-10 fold. Recent studies demonstrate that after an inflammatory stimulus, fibrinogen gene expression and protein production is upregulated in lung epithelial cells, where it is secreted basolaterally and consequently deposited into the extracellular matrix in fibrils that extensively colocalize with fibronectin fibrils. In this study, we show that the deposition of fibrinogen into the matrix of fibroblasts occurred rapidly and in a Rho-dependent manner in response to serum or lysophosphatidic acid; RhoA GTPase signaling is also required for fibronectin matrix assembly. Using mouse embryonic fibronectin-null cells, we show that incorporation of exogenous fibrinogen into matrix fibrils occurred only in the presence of exogenous fibronectin, which is also assembled into matrix fibrils. Furthermore, treatment of fibroblasts and fibronectin-null cells with an antibody that inhibits fibronectin matrix assembly impaired incorporation of fibrinogen into matrix fibrils. Collectively, these data suggest that incorporation of fibrinogen into the extracellular matrix requires active fibronectin polymer elongation into matrix fibrils. From these data, we hypothesize that fibrinogen deposition rapidly changes the topology of the extracellular matrix to provide a surface for cell migration and matrix remodeling during tissue repair.
Pereira
Marian
M
Department of Medicine-Vascular Medicine Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Rybarczyk
Brain J
BJ
Odrljin
Tatjana M
TM
Hocking
Denise C
DC
Sottile
Jane
J
Simpson-Haidaris
Patricia J
PJ
D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001905:Botulinum Toxins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D007457:Iodine Radioisotopes; D008246:Lysophospholipids; D005340:Fibrinogen; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins