Transgenic Mice Reveal Novel Activities of Growth Hormone in Wound Repair, Angiogenesis, and Myofibroblast Differentiation

• Published in: The Journal of biological chemistry Vol. 279; no. 25; pp. 26674 - 26684
• Main Authors: Thorey, Irmgard S., Hinz, Boris, Hoeflich, Andreas, Kaesler, Susanne, Bugnon, Philippe, Elmlinger, Martin, Wanke, Rüdiger, Wolf, Eckhard, Werner, Sabine
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.06.2004; American Society for Biochemistry and Molecular Biology
• Subjects: Acetic Acid - metabolism; Animals; Blotting, Western; Cell Differentiation; Collagen - metabolism; Down-Regulation; Female; Fibroblasts - cytology; Growth Hormone - genetics; Growth Hormone - metabolism; Growth Hormone - physiology; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - metabolism; Ligands; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Muscles - cytology; Neovascularization, Physiologic; Radioimmunoassay; Sex Factors; Transforming Growth Factor beta - metabolism; Wound Healing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M311467200

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 β-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.