Tissue fibrosis, or scar formation, is the common final pathway of virtually all chronic diseases and affects nearly every organ, including kidney, heart, lung, bone marrow and liver, among others. Myofibroblasts are the cells that cause fibrosis but their cellular origin has been controversial and their mechanism of activation has been unclear. We have identified Gli1+ cells as a major source of fibrosis driving myofibroblasts and demonstrated that GLi2 protein is a major driver of their expansion. Genetic ablation of these cells ameliorates fibrosis and rescues organ function. Pharmacologic inhibition of Gli proteins halts myofibroblast cell-cycle progression and ameliorates fibrosis. In conclusion our data indicates that Gli1+ perivascular cells are a promising therapeutic target in fibrosis.

Additional Metadata
Keywords Kidney fibrosis, CKD, Gli1, pericytes, myofibroblasts
Promotor R. Zietse (Bob) , E.J. Hoorn (Ewout)
Publisher Erasmus University Rotterdam
ISBN 7104388905162
Persistent URL hdl.handle.net/1765/116446
Citation
Kramann, R.J.T. (2019, May 8). Untangling cellular and molecular mechanisms of fibrotic disease. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/116446