A role for endogenous glucocorticoids in wound repair.
Exogenous glucocorticoids are known to inhibit wound repair, but the roles and mechanisms of action of endogenous glucocorticoids during the healing process are as yet unknown. Therefore, we wounded mice expressing a DNA-binding-defective mutant version of the glucocorticoid receptor (GR(dim) mice) and also analysed fibroblasts from these animals in vitro. We found a remarkably enlarged granulation tissue with a high fibroblast density in GR(dim) mice. This difference is likely to result from an increased migratory and proliferative capacity of GR(dim) fibroblasts and from elevated expression levels of soluble factors involved in granulation tissue formation in wounds of GR(dim) mice. In spite of the larger granulation tissue seen in early wounds, late wounds appeared normal, most likely due to an enhanced ability of GR(dim) fibroblasts to contract collagen. These results demonstrate an as yet unidentified role of endogenous glucocorticoids in the regulation of wound repair.
Grose
Richard
R
Institute of Cell Biology, Department of Biology, ETH Zürich, CH-8093 Zürich, Switzerland.
Werner
Silke
S
Kessler
Daniela
D
Tuckermann
Jan
J
Huggel
Katharina
K
Durka
Silke
S
Reichardt
Holger M
HM
Werner
Sabine
S
D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005938:Glucocorticoids / Q000502:physiology*; D006097:Granulation Tissue / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005938:Glucocorticoids; D006133:Growth Substances; D007375:Interleukin-1; D011965:Receptors, Glucocorticoid; D016212:Transforming Growth Factor beta