Ghrelin prevents the development of dermal fibrosis in bleomycin-induced scleroderma

Abstract

Scleroderma is a chronic inflammatory disease characterized by widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide hormone produced by various tissues and inflammatory cells. In experimental studies, ghrelin has been shown to have anti-inflammatory and antioxidant effects, in addition to its metabolic actions. To evaluate the potential preventive effects of ghrelin on a mouse model of bleomycin (BLM)-induced scleroderma. This study involved five groups of BALB/c mice (n = 7 in each group). Mice in the control group received 100 μL/day of phosphate-buffered saline (PBS) subcutaneously, while the other four groups were given 100 μg/day of BLM (dissolved in 100 μL PBS) subcutaneously. Three of the BLM-treated groups received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total ghrelin. Animals were killed at the end of the fourth week, and blood and tissue samples were collected for further analysis. Dermal thickness, serum levels of transforming growth factor-β1, numbers of inflammatory cells on the dermal layer and numbers of α-smooth muscle actin-positive cells were determined. BLM increased dermal thickness, numbers of inflammatory cells on the dermal layer and activity of the myofibroblastic cells. Application of acylated, nonacylated and total ghrelin decreased the infiltration of inflammatory cells and the activity of the myofibroblastic cells, and reduced dermal fibrosis. Based on these results, it appears that ghrelin has an antifibrotic action, in addition to the anti-inflammatory and antioxidant effects that have been documented previously. The pathogenic and therapeutic roles of ghrelin in scleroderma should be evaluated by further studies.