Roles of RhoA and Rac1 on actin remodeling and cell alignment and differentiation in fetal type II epithelial cells exposed to cyclic mechanical stretch.
Mechanical forces are critical for normal fetal lung development. However, the signaling events that promote lung maturation are not fully understood. In this study, the authors analyzed the role of Rho family guanidine triphosphatases (GTPases) in isolated embryonic day 19 (E19) fetal type II epithelial cells exposed to 5% cyclic stretch. The results showed that mechanical strain stimulated RhoA within 5 minutes of initiation of force. Rac1 was also activated, but not Cdc42. After 6 hours of equibiaxial stretch, actin filaments were oriented parallel to the long axis of the cells. By 16 hours, actin fibers still maintained the same orientation, but their intensity decreased when compared to 6 hours. These findings temporally correlated with a decrease in RhoA stimulation. Using adenoviruses encoding dominant negative mutants of RhoA and Rac1, the authors observed that both GTPases are important for strain-induced stress fiber formation, cell alignment, and extracellular signal-regulated kinase (ERK) phosphorylation. However, whereas inhibition of Rho increased surfactant protein C (SP-C) mRNA expression (a marker of type II cell differentiation), suppression of Rac had no effects. These studies suggest that RhoA and Rac1 regulate actin remodeling and cell alignment in fetal type II cells exposed to mechanical stretch. RhoA is a negative regulator of stretch-induced type II cell maturation.
Silbert
Ophira
O
Department of Pediatrics, Women & Infants Hospital of Rhode Island and the Warren Alpert Medical School of Brown University, Providence, Rhode Island 02905, USA.
Wang
Yulian
Y
Maciejewski
Benjamin S
BS
Lee
Hyeon-Soo
HS
Shaw
Sunil K
SK
Sanchez-Esteban
Juan
J
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D008168:Lung / Q000196:embryology*; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D000199:Actins; D048049:Extracellular Signal-Regulated MAP Kinases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein