CREB family: A significant role in liver fibrosis

Abstract

Liver fibrosis (LF) is known as a result of the progressive accumulation of extracellular matrix (ECM), and always ascribed to chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, portal hypertension, and even multi-organ dysfunction and will bring up a health care burden worldwide. Cyclic AMP response-element binding protein (CREB), as a critical transcriptional factor, binds with conserved cAMP response-element (CRE), which is located in the promoter of targeted genes, to regulate the transcription. In the past decades, numerous studies have contributed to improved understanding of the links between CREB and liver fibrosis. In this review, we will summarize molecular mechanisms of CREB pathways and discuss contributions of CREB to liver fibrosis, focusing on activation and proliferation of hepatic stellate cells (HSCs), proliferation of cholangiocytes, deposition of extracellular matrix (ECM) and inflammation, for the development of antifibrotic therapies.

Keywords: Cholangiocytes; Extracellular matrix (ECM); Hepatic stellate cells (HSCs); Inflammation; Liver fibrosis (LF); cAMP response-element binding protein (CREB).