ED-A Fibronectin: A Storage Site for Latent TGFB-1 in the Myofibroblast Matrix?

• Main Author: Chau, Grace
• Other Authors: Hinz, Boris
• Language: en_ca
• Published: 2012
• Subjects: biology; 0306
• Online Access: http://hdl.handle.net/1807/32532

Fibrosis, a major cause of organ failure, has no effective therapy available. Responsible for fibrosis are myofibroblasts. Mechanical stress, TGF myofibroblast differentiation, however the exact link remains elusive. I hypothesize that ED-A FN stores the latent TGF -1 in the ECM by interacting with the latent TGF -1 binding protein (LTBP-1), and that matrix stiffness is a regulator of ED-A FN and LTBP-1. Using co-IP and ED-A domain antagonists, ED-A FN and LTBP-1 associated in the ECM of human dermal fibroblasts (HDFs). The effects of the 11th_ED-A_12th recombinant FN peptide was most prominent in blocking LTBP-1 incorporation in the ECM. HDFs seeded on collagen- coated substrates, showed an increase in expression and organization for both proteins with matrix stiffness. In conclusion, the ED-A domain may require the aid of heparin linkages flanking the 12th domain of FN to bind to LTBP-1 in the ECM.