CXC chemokines as Molecular Targets for Future Diagnosis and (Renal) Fibrosis Treatment

Renal fibrosis is the final common pathway of chronic kidney disease (CKD), which ultimately leads to end-stage renal disease (ESRD) demanding renal replacement therapy. As such, renal fibrosis is an increasing global health problem. As yet, no adequate preventive or curative therapy is available that can be clinically used to target the development of fibrosis. Chemokines are chemotactic cytokines that are well-known for their ability to direct the migration and activation of inflammatory cells. In the field of fibrosis, attention has recently been paid to chemokines and their role in (myo)fibroblast proliferation and activation. The latter cells are key pathogenic cells during fibrosis. However, the mechanisms behind the fibrotic or anti-fibrotic effects of chemokines are largely unknown. Both interactions with G protein-coupled receptors and glycosaminoglycans may play a role and also posttranslational chemokine modification by specific chemokine-modifying enzymes may affect the final outcome. With this project we wish to investigate in depth the mechanisms by which chemokines affect fibrosis and we wish to set up an in vitro screening assay to identify natural molecules which modify fibrosis. With this research project we wish to move forward in the search for inhibitors of fibrosis in general and renal fibrosis in particular. In the long term, this should lead to novel therapies for instance for the treatment of patients who progress to ESRD.