Profibrotic impact of TGF-β1 on gene expression in primary mouse hepatocytes

Transforming growth factor beta 1 (TGF-β1) is a key effector cytokine in liver fibrosis. Although the intense investigations, the mechanisms of liver fibrosis remain elusive. In this study, we aimed to identify signaling pathways that are differentially regulated upon TGF-β1 stimulation and might serve as markers for enhanced pathophysiological level of TGF-β1 in liver. By a genome-wide gene expression profiling, we identified 2,196 differentially regulated genes. Using KEGG and David tools, the TGF-β1 gene targets were mapped into annotated pathways, revealing relationships broadly altered in primary mouse hepatocytes (TGF-β, Wnt, MAPK and Notch signaling as well as ErbB, PPAR, insulin and Toll-like receptor signaling pathways). Further, by blocking the TGF-β type I receptor (ALK-5) with SB431542, ALK-5 dependent and independent TGF-β1-responsive genes were discriminated. We conclude that robust genome wide transcriptome analyses of TGF-β1 treated mouse hepatocytes provide an overall signature of the impact of this cytokine, allowing previously unexpected functional predictions. Furthermore, disturbing the system by shutting off specific branches of the pathway may help to identify function/disease related components/steps with drugable potential.

TGF-β1 - fibrosis - hepatocyte - liver - microarray - signaling