Endocrine Abstracts

Idiopathic pulmonary fibrosis (IPF) is an excessive accumulation of fibrous filaments in the extracellular matrix (ECM), in response to an inflammatory reaction that disrupts normal lung architecture and physiology. Collagen is the most abundant fibrous protein in the ECM. The GLP-1 receptor is highly expressed on lung tissue, where his activation plays an essential role in the synthesis and secretion of surfactant proteins. The objective of this study was to elucidate the effect of Liraglutide treatment on collagen synthesis and deposition in the lungs of an animal model of IPF. IPF was induced in male rats by a single intra tracheal instillation of bleomycin (BLM, 2.5 mg/kg) on day 0. Animals were treated with Liraglutide at a dose of LIR, 100 μg/kg per 12 h subcutaneous, using two different protocols. 1-Preventive treatment: LIR treatment was given from day-1 to day 6 and animals were sacrificed in day 7 and day 21. 2-Therapeutic intervention: animals were treated from day 10 to day 20 after BLM; and animals were sacrificed on day 21. Lung lobes were isolated and frozen for mRNA expression analysis by Real time PCR, and for hydroxyproline quantification and Arginase-1 activity testing. We obtained Broncho alveolar lavage liquid for analysis of soluble collagen. The mRNA expression of Collagen type 1 and the enzymes Arginase-1 and prolyl hydroxylase, which are essential for collagen fibre synthesis, were increased at day 7 and day 21 in BLM instilled animals. Tissue levels of hydroxyproline were very increased just at day 21, in the fibrotic phase. LIR treatment normalized the mRNA expression levels of the two enzymes at the times studied. In addition, LIR administration decreased day 21 type I collagen mRNA expression and total collagen deposition on lung tissue, as well the soluble collagen in alveolar lavage liquid. In conclusion, incretins play an important role in the regulation of the synthesis and activity of key enzymes in the formation of collagen fibres and deposition. Since, incretins may be useful molecules in the treatment and prevention of the pulmonary tissue fibrotic processes.