The key role of alpha-SMA in myofibroblast function for liver injury
Tissue injury leads to a wound healing response by the body, characterized by fibrogenesis as well as wound contraction. A key feature of the cellular response to injury is the appearance of a population of specialized cells known as myofibroblasts. Myofibroblasts are cells that have contractile properties and are involved in inflammation, wound healing, fibrosis, and oncogenesis in most organs and tissues. They are involved in healing and granulation tissue formation that occur after tissue injuries. They also produce inflammatory mediators, growth factors, and help reorganize the extracellular matrix.In the liver, injury and the subsequent wound response lead to the activation of resident cells known as hepatic stellate cells. Once activated, these cells undergo a cascade of events leading to tissue remodeling and healing. This very complex process involves specific cellular responses and cell proliferation, as well as cell motility and contractility. Among all the cellular components involved in this process, α-Smooth Muscle Actin (alpha-SMA or Acta2) plays a key role.Using a full range of techniques, including Western-Blot, 2D-PAGE, antisense oligonucleotides, immunohistochemistry, and migration assays, Don C. Rockey deciphered the roles of Acta2 in stellate cell contractility and motility. He went one-step further by showing the links between Acta2 and ERK pathway activation.α-Smooth Muscle Actin (Acta2) is clearly a proven marker for assessing myofibroblast differentiation and phenotype. A key marker involved in wounding processes and fibrogenesis. After reading this article, you will better understand the physiological roles of Acta2 during hepatic wound healing.Don’t hesitate to set up your own in-vitro assay!
Smooth muscle α actin (Acta2) expression is largely restricted to smooth muscle cells, pericytes and specialized fibroblasts, known as myofibroblasts. Liver injury, associated with cirrhosis, induces transformation of resident hepatic stellate cells into liver specific myofibroblasts, also known as activated cells. Here, we have used in vitro and in vivo wound healing models to explore the functional role of Acta2 in this transformation. Acta2 was abundant in activated cells isolated from injured livers but was undetectable in quiescent cells isolated from normal livers. Both cellular motility and contraction were dramatically increased in injured liver cells, paralleled by an increase in Acta2 expression, when compared with quiescent cells. Inhibition of Acta2 using several different techniques had no effect on cytoplasmic actin isoform expression, but led to reduced cellular motility and contraction. Additionally, Acta2 knockdown was associated with a significant reduction in Erk1/2 phosphorylation compared to control cells. The data indicate that Acta2 is important specifically in myofibroblast cell motility and contraction and raise the possibility that the Acta2 cytoskeleton, beyond its structural importance in the cell, could be important in regulating signaling processes during wound healing in vivo.
PLoS One. 2013 Oct 29; Vol. 8 (10): e77166.