Transgenic mice reveal novel activities of growth hormone in wound repair, angiogenesis, and myofibroblast differentiation.
An increasing number of patients are being treated with growth hormone (GH) for the enhancement of body growth but also as an anti-aging strategy. However, the side effects of GH have been poorly defined. In this study we determined the effect of GH on wound repair and its mechanisms of action at the wound site. For this purpose, we performed wound healing studies in transgenic mice overexpressing GH. Full thickness incisional and excisional wounds of transgenic animals developed extensive, highly vascularized granulation tissue. However, wound bursting strength was not increased. Wound closure was strongly delayed as a result of enhanced granulation tissue formation and impaired wound contraction. The latter effect is most likely due to a significantly reduced number of myofibroblasts at the wound site. By using in vitro studies with stressed collagen lattices, we identified GH as an inhibitor of transforming growth factor beta-induced myofibroblast differentiation, resulting in a reduction in fibroblast contractile activity. These results revealed novel roles of GH in angiogenesis and myofibroblast differentiation, which are most likely not mediated via insulin-like growth factors at the wound site. Furthermore, our data suggested that systemic GH treatment is detrimental for wound healing in healthy individuals.
Thorey
Irmgard S
IS
Institute of Cell Biology, Department of Biology, ETH Zurich, Honggerberg, CH-8093 Zurich, Switzerland.
Hinz
Boris
B
Hoeflich
Andreas
A
Kaesler
Susanne
S
Bugnon
Philippe
P
Elmlinger
Martin
M
Wanke
Rüdiger
R
Wolf
Eckhard
E
Werner
Sabine
S
D019342:Acetic Acid / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000166:cytology*; D018919:Neovascularization, Physiologic; D011863:Radioimmunoassay; D012737:Sex Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
D018971:Insulin-Like Growth Factor Binding Protein 2; D008024:Ligands; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D003094:Collagen; D019342:Acetic Acid