SRF/MRTF‐A and liver cirrhosis: Pathologic associations

Abstract

Liver cirrhosis results from prolonged and extensive liver fibrosis in which fibrotic tissues replace functional hepatic cells. Chronic liver disease due to various viral, chemical, or metabolic factors initiates hepatic fibrogenesis. Cirrhosis is associated with multiple clinical complications and a poor patient prognosis; therefore, developing novel antifibrotic therapies to prevent cirrhosis is of high priority. Mounting evidence points to the key role of serum response factor (SRF) and myocardin‐related transcription factor (MRTF)‐A in the pathogenesis of liver fibrosis. SRF is a transcription factor and MRTF‐A is a co‐activator of SRF and normally resides in the cytoplasm. Upon the induction of fibrotic pathways, MRTF‐A translocates into the nucleus and forms the active SRF/MRTF‐A complex, leading to the expression of a multitude of fibrotic proteins and components of extracellular matrix. Silencing or inhibiting MRTF‐A impedes hepatic stellate cell transdifferentiation into myofibroblasts and slows down the deposition of extracellular matrix in the liver, making it a potential therapeutic target. Here, we review the recent findings regarding the role of the SRF/MRTF‐A complex in liver fibrosis and its therapeutic potential for the management of cirrhosis.