Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

Abstract

Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

• Authors: Nikolina Dioufa, Andrew V Schally, Ioulia Chatzistamou, Evi Moustou, Norman L Block, Gary K Owens, Athanasios G Papavassiliou, Hippokratis Kiaris
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 43 Pg. 18611-5 (Oct 26 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 20937882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• JI-38
• alpha-smooth muscle actin, mouse
• Growth Hormone-Releasing Hormone

Topics

• Actins (genetics)
• Animals
• Cell Movement (drug effects)
• Cells, Cultured
• Fibroblasts (drug effects, physiology)
• Gene Expression (drug effects)
• Growth Hormone-Releasing Hormone (agonists, analogs & derivatives, pharmacology, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Wound Healing (drug effects, genetics, physiology)