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PMID: 11553712 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alpha-smooth muscle actin expression upregulates fibroblast contractile activity.

Molecular biology of the cell ·Vol. 12 ·No. 9 ·2001-09-00 ·Pages 2730-41

Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C

Abstract

To evaluate whether alpha-smooth muscle actin (alpha-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of alpha-SMA, with that of lung fibroblasts (LFs), expressing high levels of alpha-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of alpha-SMA-positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for alpha-SMA. In a second approach, we measured the isotonic contraction of SCF- and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGFbeta1 increased alpha-SMA expression and lattice contraction by SCFs to the levels of LFs; TGFbeta-antagonizing agents reduced alpha-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with alpha-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with alpha-cardiac and beta- or gamma-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased alpha-SMA expression is sufficient to enhance fibroblast contractile activity.

MeSH Terms
3T3 Cells Actins/genetics,metabolism Animals Blotting, Western Cell Size/drug effects Cells, Cultured Collagen/metabolism Fibroblasts/cytology,drug effects,metabolism Gels Mice Microscopy, Fluorescence Muscle, Smooth/metabolism Protein Isoforms/genetics,metabolism Rats Silicon/metabolism Transfection Transforming Growth Factor beta/pharmacology Up-Regulation
Chemicals
Actins Gels Protein Isoforms Transforming Growth Factor beta Collagen Silicon
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hinz B
Department of Pathology, CMU, University of Geneva, 1211 Geneva 4, Switzerland.
Celetta G
Tomasek J J
Gabbiani G
Chaponnier C
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.12.9.2730
Published
2001-09-00
Pages
2730-41
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC59708
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.12.9.2730 PMC Full Text View journal details
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