ABSTRACT The healing of wounds is controlled by general processes associated with the endocrine, nervous and immunological systems and local factors, such as mediators of inflammation, chemokines or growth factors. The aim of the present study is to analyze the recently published data concerning the regulatory role of the pineal gland in repair and fibrosis. Healing of the circular and incised linear wounds in the skin or intestine is inhibited by melatonin the hormone of the pineal gland. The opposite effect of pinealectomy can be reversed by melatonin application. In both intestinal wounds and sponge induced granuloma, collagen accumulation is inhibited by the pineal gland. Melatonin or continuous darkness are also able to reduce liver fibrosis caused by alcohol. Pinealectomy induces fibrosis of the retroperitoneal space. On the contrary, melatonin administration at a dose dependent manner increased accumulation of collagen in the myocardial infarction scar. Removal of the pineal gland or pharmacological blockade of the pineal gland by treatment with β-blocker decreases collagen content in the myocardial scar (this effect can be reversed by melatonin application). The reviewed studies clearly indicate that healing processes are regulated by the pineal gland and melatonin, the effect being dependent on the target organ. Hence, melatonin inhibits collagen accumulation and repair in the superficial and intestinal wounds as well as in sponge induced granuloma and liver. Contrary to that, melatonin enhances collagen deposition in the myocardial scar and osteoblast cultures. The final effect of melatonin is dependent on the target organ, time of melatonin application and applied dose. The mechanisms of melatonin action cannot be fully explained in the light of the present data, however two possible melatonin influences should be taken into consideration: a direct effect of melatonin on the cells which synthetize collagen (myofibroblasts, osteoblasts) and an indirect one on the collagen metabolism via general regulatory mechanisms (immune, nervous and endocrine).
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