p70 Ribosomal Protein S6 Kinase Is a Checkpoint of Human Hepatic Stellate Cell Activation and Liver Fibrosis in Mice
Florian P. Reiter, Liangtao Ye, Andrea Ofner, Tobias S. Schiergens, Andreas Ziesch, Lydia Brandl, Najib Ben Khaled, Simon Hohenester, Ralf Wimmer, Renate Artmann, Yulong He, Serene M. L. Lee, Doris Mayr, Changhua Zhang, Alexander L. Gerbes, Julia Mayerle, Gerald Denk, Enrico N. De Toni
Abstract
BACKGROUND & AIMS: Progression of chronic liver disease (CLD) to liver cirrhosis and liver cancer is a major global cause of morbidity and mortality. Treatment options capable of inhibiting progression of liver fibrosis when etiological treatment of CLD is not available or fails have yet to be established. We investigated the role of serine/threonine kinase p70 ribosomal protein S6 kinase (p70S6K) as checkpoint of fibrogenesis in hepatic stellate cells (HSCs) and as target for the treatment of liver fibrosis. APPROACH & RESULTS: . CONCLUSIONS: We establish p70S6K as a checkpoint of fibrogenesis in vitro and in vivo and CEP-1347 as potential treatment option that can safely be used for long-term treatment.