Transcriptional regulation in hepatic stellate cells.

Abstract

Modulation of gene expression through altered transcription regulates stellate cell behavior in normal liver and following hepatic injury. Transcription factors are generally classified according to conserved motifs within either the activation- or DNA- binding domains of the molecules. Transcriptional activity in stellate cells represents a delicate fine tuning of multiple inputs. Activities of these transcription factors are modified by their intracellular localization, rate and pathway of degradation, oligomerization, and interactions with heterologous factors and chromatin, as well as by posttranslational modifications, including phosphorylation, glycosylation, and acetylation. General paradigms of transcriptional control are increasingly being validated in hepatic stellate cells, particularly involving the transcription factors CCAAT/enhancer-binding proteins, c-myb, CREB, nuclear factor kappaB, peroxisome proliferator-activated receptor, and Kruppel-like zinc finger factors. Although there are no simple rules that govern mechanisms of transcriptional regulation in stellate cells, continued advances will yield new insights into their role in normal liver homeostasis and in the response to injury.