title: Cryptic activity within the Type III1domain of fibronectin regulates tissue inflammation and angiogenesis.
abstract: The fibronectin matrix provides mechanical and biochemical information to regulate homeostatic and pathological processes within tissues. Fibronectin consists of independently-folded modules termed Types I, II and III. In response to cellular contractile force, Type III domains unfold to initiate a series of homophilic binding events which result in the assembly of a complex network of intertwining fibrils. The unfolding of Type III modules provides elasticity to the assembled fibronectin matrix allowing it to function as a dynamic scaffold which provides binding sites for cellular receptors, growth factors and other matrix molecules. Access to bioactive sites within the fibronectin matrix is under complex regulation and controlled through a combination of mechanical and proteolytic activity. Mechanical unfolding of Type III modules and limited proteolysis can alter the topographical display of bioactive sites within the fibronectin fibrils by exposing previously cryptic sites and disrupting functional sites. In this review we will discuss cryptic activity found within the first Type III module of fibronectin and its impact on tissue angiogenesis and inflammation.
authors.affiliation: Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Cho
authors.affiliation: Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Kelsh-Lasher
authors.affiliation: Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ambesi
authors.affiliation: Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: McKeown-Longo
keywords: Toll-like receptor; Type III domain; VEGF; anastellin; angiogenesis; fibronectin; inflammation; matrix assembly