Role of vimentin in smooth muscle force development.
Vimentin intermediate filaments undergo spatial reorganization in cultured smooth muscle cells in response to contractile activation; however, the role of vimentin in the physiological properties of smooth muscle has not been well elucidated. Tracheal smooth muscle strips were loaded with antisense oligonucleotides (ODNs) against vimentin and then cultured for 2 days to allow for protein degradation. Treatment with vimentin antisense, but not sense, ODNs suppressed vimentin protein expression; neither vimentin antisense nor sense ODNs affected protein levels of desmin and actin. Force development in response to ACh stimulation or KCl depolarization was lower in vimentin-deficient tissues than in vimentin sense ODN- or non-ODN-treated muscle strips. Passive tension was also depressed in vimentin-depleted muscle tissues. Vimentin downregulation did not attenuate increases in myosin light chain (MLC) phosphorylation in response to contractile stimulation or basal MLC phosphorylation. In vimentin sense ODN-treated or non-ODN-treated smooth muscle strips, the desmosomal protein plakoglobin was primarily localized in the cell periphery. The membrane-associated localization of plakoglobin was reduced in vimentin-depleted muscle tissues. These studies suggest that vimentin filaments play an important role in mediating active force development and passive tension, which are not regulated by MLC phosphorylation. Vimentin downregulation impairs the structural organization of desmosomes, which may be associated with the decrease in force development.
Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Avenue MC-8, Albany, NY 12208, USA.
Ruping
R
Wang
Qingfen
Q
Li
Dale D
DD
Tang
D000109:Acetylcholine / Q000378:metabolism; D000199:Actins / Q000032:analysis / Q000235:genetics; D000818:Animals; D003893:Desmin / Q000032:analysis / Q000235:genetics; D004285:Dogs; D015536:Down-Regulation; D066298:In Vitro Techniques; D007537:Isometric Contraction; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D018994:Myosin Light Chains / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D010766:Phosphorylation; D011189:Potassium Chloride; D014132:Trachea / Q000166:cytology; D014746:Vimentin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051185:gamma Catenin / Q000032:analysis
D000199:Actins; D003893:Desmin; D018994:Myosin Light Chains; D016376:Oligonucleotides, Antisense; D014746:Vimentin; D051185:gamma Catenin; D011189:Potassium Chloride; D000109:Acetylcholine