Mendoza-Marí Y, Fernández-Mayola M, Vázquez-Blomquist D, García-Ojalvo A, Suárez-Alba J, Guillén-Nieto G, Aguilera-Barreto A, Bermúdez-Álvarez Y, Ugarte D, del Barco-Herrera DG, López-Mola E, Selman-Hussein M, Berlanga-Acosta J

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ABSTRACT

Fibrosis is defined as the pathological accumulation of extracellular matrix proteins (ECM) during the tissue repair response to an injury, which interferes with the functioning of the damaged organ or tissue. So far, there are no effective preventive or curative treatments. The growth hormone-releasing peptide 6 (GHRP-6) has anti-inflammatory, anti-oxidant and cytoprotective properties. Early signs of its possible anti-fibrotic effect were observed in a model of dilated cardiomyopathy in rats. This new property of the peptide was first studied in a model of liver cirrhosis in rats, in preventive and therapeutic scenarios. GHRP-6 reduced fibrotic induration in more than 75%, cords thickness and number of cirrhotic nodules by up to 60%, exerting besides a marked hepatoprotective effect. To assess its effect on the skin, GHRP-6 was applied in a simple wound model in rats, where it increased the rate of wound closure and decreased the inflammatory infiltrate. Subsequently, in a model of hypertrophic scarring in rabbits, the peptide prevented the appearance of keloids in more than 90% of the treated wounds. From the molecular point of view, GHRP-6 decreased the transcriptional expression of the pro-fibrotic genes TGFB1 and CTGF and induced the expression of the PPARG and MMP-13 genes, relevant for the inhibition of the pathological cumulative process. This work received the Annual Prize of the Cuban Academy of Sciences for the year 2016.