Abstract
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.
Highlights
Actin plays an important role in many cellular processes, including cell division, cell motility and the generation of contractile force
We evaluated cell motility in Acta2 deficient mouse embryo fibroblasts (MEFs) and in stellate cells isolated from these mice
We show here that in vivo stellate cell activation after liver wounding is associated with a striking increase in cellular motility and contractility; this functional transition parallels an increase in expression of Acta2, typical of myofibroblasts
Summary
Actin plays an important role in many cellular processes, including cell division, cell motility and the generation of contractile force. Two nonmuscle or cytoplasmic actins, b and c, are found in all cells while the muscle actins include c smooth muscle actin, and 3 a actin variants (smooth, cardiac and skeletal), each of which is restricted to specialized muscle or muscle-like cells [3,4]. Despite the fact that the 6 known eukaryotic actin isoforms are coded for by 6 different genes, the actins exhibit remarkable amino acid similarity [8]. A weak interaction between actin and myosin which appears to be dependent on the negatively charged aminoterminal region of actin and the positively charged flexible loop on the myosin head [11] raises the possibility that differences in actin structure in the amino-terminal region could lead to divergent functional characteristics of the actins
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
