Differences in the Regulation of Fibroblast Contraction of Floating Versus Stressed Collagen Matrices*
- From the Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical School, Dallas, Texas 75235
Abstract
To learn more about the regulation of contraction of collagen matrices by fibroblasts, we compared the ability of lysophosphatidic acid (LPA) and platelet-derived growth factor (PDGF) to stimulate contraction of floating and stressed collagen matrices. In floating collagen matrices, PDGF and LPA stimulated contraction with similar kinetics, but appeared to utilize complementary signaling pathways since contraction obtained by the combination of growth factors exceeded that observed with saturating concentrations of either alone. The PDGF-simulated pathway was selectively inhibited by the protein kinase inhibitor KT5926. In stressed collagen matrices, PDGF and LPA stimulated contraction with different kinetics, with LPA acting rapidly and PDGF acting only after an ∼1-h lag period. Pertussis toxin, known to block signaling through the Gi class of heterotrimeric G-proteins, inhibited LPA-stimulated contraction of floating but not stressed matrices, suggesting that LPA-stimulated contraction depends on receptors coupled to different G-proteins in floating and stressed matrices. On the other hand, the Rho inhibitor C3 exotransferase blocked contraction of both floating and stressed collagen matrices. These results suggest the possibility that distinct signaling mechanisms regulate contraction of floating and stressed collagen matrices.
Footnotes
-
↵* This work was supported by National Institutes of Health Grant GM31321.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵‡ To whom correspondence should be addressed: Dept. of Cell Biology and Neuroscience, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75235. Tel.: 214-648-2181; Fax: 214-648-8694; E-mail: grinne01{at}utsw.swmed.edu.
- Abbreviations:
- PDGF
-
platelet-derived growth factor
- DMEM
-
Dulbecco’s modified Eagle’s medium
- FBS
-
fetal bovine serum
- PTx
-
pertussis toxin
- C3
-
C3 exotransferase
- LPA
-
lysophosphatidic acid
- MLC
-
myosin light chain.
-
- Received July 15, 1998.
- Revision received October 13, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
