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.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32532 |
| Date | 24 July 2012 |
| Creators | Chau, Grace |
| Contributors | Hinz, Boris |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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