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

作者：Dioufa Nikolina; Schally Andrew V^*; Chatzistamou Ioulia; Moustou Evi; Block Norman L; Owens Gary K; Papavassiliou Athanasios G; Kiaris Hippokratis

来源：Proceedings of the National Academy of Sciences, 2010, 107(43): 18611-18615.

DOI：10.1073/pnas.1013942107

• smooth muscle
• actin
• fibroblast proliferation
• growth hormone

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 100nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of alpha-smooth muscle actin (alpha SMA) based on immunoblot analyses as well as the expression of an alpha SMA-beta-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of alpha SMA 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.

• 出版日期2010-10-26