Project 4

Project 4: The role of Heparan Sulfate 3-O-sulfation in chronic renal fibrosis

Heparan Sulfate modifies its sulphation patterns in response to inflammation which results in increased binding to growth factors and chemokines and that leads to fibrosis initiation; inhibition of their interaction alters leukocytes infiltration and matrix remodeling. My main objective is to examine the role of HS 3-O-sulfation in fibrosis. In order to assess the sulfated Heparan Sulfate patterns binding affinity to FGF2 a range of FGF2 peptides were generated. During secondment to Durham University Isothermal titration Calorimetry (ITC) techniques was used to study their binding to HS. Future work will determine whether these peptides can inhibit the interaction between FGF2 and HS. Furthermore, stable transfectants of kidney epithelial cells expressing HS3-O-sulphation were generated. These transfectants are being used to examine the role of 3-O sulfation in FGF2 binding and renal fibrosis.

Further reading: L. Ferreras, N. S. Sheerin, J. A. Kirby, S. Ali, Mechanisms of Renal Graft Chronic Injury and Progression to Interstitial Fibrosis. Curr Transpl Rep (2015) 2:259–268