Transcriptional activity of Serum Response Factor is mediated by the RhoA/Rho kinase pathway during HSC differentiation and influences expression of Smooth Muscle Cell marker genes

Hepatic stellate cells (HSC) are prominent cellular effectors of liver fibrosis, which become activated during liver injury and transdifferentiate from quiescent, fat storing cells into a proliferative myofibroblastic cell type (MFB). This process is accompanied by modulations of gene expression. A common feature of activated HSC is upregulation of genes encoding known markers of smooth muscle cells (SMC), e.g. α-smooth muscle actin (α-SMA). In SMC, these genes are regulated by the ubiquitous transcription factor serum response factor (SRF) in cooperation with specific co-factors, especially myocardin. As SRF becomes strongly expressed in activated HSC, we looked for its transcriptional activity at different time points of differentiation and factors involved in this process.