Lysophosphatidic acid augments fibroblast-mediated contraction of released collagen gels.
Lysophosphatidic acid (LPA) is a glycerophospholipid released from platelets that has multiple biologic effects. The present study evaluated the potential of LPA to modulate tissue repair and remodeling by modifying human lung fibro-blast-mediated contraction of three-dimensional collagen gels. The contraction of native collagen gels caused by human fetal lung fibroblasts was augmented by LPA in a concentration-dependent manner. The estimated median effective concentration was 3 x 10(-7) mol/L, which was well below the concentrations likely released by platelets in tissues. LPA-augmented contraction was not blocked by pertussis toxin or cholera toxin but was inhibited by inhibition of phospholipase C. Neither calcium mobilization nor protein kinase C appeared to play a role. In contrast, the effect of LPA appeared to depend on a kinase inhibited by staurosporine but not by genistein or GF109203X, suggesting a process that depends on phospholipase C and may involve a novel protein kinase. By modulating fibroblast-mediated remodeling, LPA could play a role in the tissue remodeling that characterizes wound repair.
Mio
Tadashi
T
Chest Disease Research Institute, Kyoto University, Japan.
Liu
Xiangde
X
Toews
Myron L
ML
Rennard
Stephen I
SI
D002118:Calcium / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D003094:Collagen / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000502:physiology*; D005782:Gels; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D005782:Gels; D008246:Lysophospholipids; D010972:Platelet Activating Factor; D047428:Protein Kinase Inhibitors; D010566:Virulence Factors, Bordetella; D003094:Collagen; D002772:Cholera Toxin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium