ABSTRACT
OBJECTIVE: The aim of this study is to investigate the effects of topical growth hormone (GH) treatment on skin wound healing in mice. MATERIALS AND METHODS: An excisional wound healing model was established on male Swiss mice, and wound healing ability was evaluated by macroscopic and histologic analyses of mice treated with topical 10-8 M and 10-7 M of GH versus the mice receiving ve- hicle alone. Wound tissues were collected on post treatment days 3, 7, and 14. Skin fragments were subjected to hematoxylin and eo- sin and Masson's trichrome staining for morphological analyses. The expression of type I collagen and platelet endothelial cell adhesion molecule 1 (CD31) was detected by immunohistochemical analysis. RESULTS: Topical treatment with GH resulted in faster wound closure rates at all time points analyzed versus those observed in the control group (day 3: 18.3 ± 3.1 vs. 44.4 ± 7.4, 43.6 ± 0.6; day 7: 41.7 ± 6.3 vs. 73.8 ± 6.6, 71.3 ± 5.8; day 12: 94.3 ± 3.9 vs. 100 ± 0, 100 ± 0). Histological analysis of the wound on post treatment day 3 revealed a more diffused in ltration of in ammatory cells in the group treated with GH. After day 7, GH-treated animals began form- ing granulation tissue, and there was an increase in in ammatory cell in ltration. The GH signi cantly increased the expression of type I collagen (day 7: 57.4 ± 4.0 vs. 120.2 ± 9.7, 79.3 ± 7.9; day 14: 218.2 ± 10.4 vs. 301.5 ± 9.1, 235.0 ± 7.5) as well as the number of blood vessels (day 7: 10.0 ± 2.4 vs. 15.3 ± 2.0, 10.1 ± 2.2; day 14: 3.2 ± 0.8 vs. 5.6 ± 2.0, 6.2 ± 2.2) in the injured area. CONCLUSIONS: The GH accelerates the closure of skin wounds by resolving the in- ammatory phase faster, accelerating reepithelialization and collagen deposition, and stimulating angiogenesis.
Subject(s)
Granulation Tissue/drug effects , Granulation Tissue/pathology , Growth Hormone/pharmacology , Skin/drug effects , Skin/pathology , Wound Healing/drug effects , Wound Healing/physiology , Administration, Topical , Animals , Cell Proliferation/drug effects , Cell Proliferation/physiology , Collagen/metabolism , Disease Models, Animal , Immunohistochemistry , Male , Mice , Neovascularization, Physiologic/drug effects , Skin/injuriesABSTRACT
The generation of new blood vessels is a complex process mediated by a variety of growth factors, and the growth hormone (GH) has been shown to act as a proangiogenic factor. In fact, human GH deficiency or excess are associated with endothelial dysfunction. Moreover, mouse models have revealed the action of GH in both tissue repair and in the microvascular circulation of normal tissues. In this study, we investigated the in vitro effects of GH on endothelial cells. Using a murine endothelioma cell line (tEnd.1), we demonstrated that GH has a mitogenic effect. The hormone also affected the endothelial cellular morphology and augmented the deposition of the extracellular matrix molecules, laminin, and fibronectin, on tEnd.1 surface. GH could stimulate tEnd.1 cell fugetaxis, in transwell chambers migration assay, and increased the formation of capillary-like structures in Matrigel®-coated plates. Given the important role of angiogenesis during tissue injury, for example, at ischemic lesions, these findings shed light on therapeutic angiogenesis, particularly in pathologies where the cardiovascular system has been compromised.
