The cellular microenvironment and cytoskeletal actin dynamics in liver fibrogenesis

Hepatic stellate cells (HSCs) are the primary effector cells in liver fibrosis. In the normal liver, HSCs serve as the primary vitamin A storage cells in the body and retain a “quiescent” phenotype. However, after liver injury, they transdifferentiate to an “activated” myofibroblast-like phenotype, which is associated with dramatic upregulation of smooth muscle specific actin and extracellular matrix proteins. The result is a fibrotic, stiff, and dysfunctional liver. Therefore, understanding the molecular mechanisms that govern HSC function is essential for the development of anti-fibrotic medications. The actin cytoskeleton has emerged as a key component of the fibrogenic response in wound healing. Recent data indicate that the cytoskeleton receives signals from the cellular microenvironment and translates them to cellular function—in particular, increased type I collagen expression. Dynamic in nature, the actin cytoskeleton continuously polymerizes and depolymerizes in response to changes in the cellular microenvironment. In this viewpoint, we discuss the recent developments underlying cytoskeletal actin dynamics in liver fibrosis, including how the cellular microenvironment affects HSC function and the molecular mechanisms that regulate the actin-induced increase in collagen expression typical of activated HSCs.

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