The efficiency of urotensin 2 antagonist in an experimental lung fibrosis model

Systemic Sclerosis (SSc) is a disease characterized by skin and internal organ involvement. Interstitial lung disease is the prominent reason for mortality and there is still any satisfactory treatment. The pathogenesis of the lung pathology is not clearly demonstrated. Urotensin-II (U-II) is a new peptide with angiogenic and pro-fibrotic features and we found this cytokine elevated and positively correlated with another important cytokine Endothelin-1(ET-1) in a previous study in our clinic in SSc patients. Therefore we aimed to evaluate the antagonism of U-II with Palosuran in an animal model and we planned to measure U-II, ET-1 and transforming growth factor-ß1 (TGF-ß1) and their association with lung fibrosis.Thirty wistar type male rats included in to the study and they were divided in 3 groups (control group, bleomycin induced lung fibrosis group, palosuran treated group).The U-II level (ng/ml) was 2.957±0.159 in control group, 3.188±0.122 in patient group and 2.970±0.165 in treatment group (p=0.002). ET-1 level (pg/ml) was 4.486±0.376 in control group, 9.086±1.850 in patient group and 4.486±0.376 in treatment group (p<0.001). TGF-ß1 (ng/ml) level was 73.143±9.96 in control group, 84.81±4.73 in patient group and 77.86±5.77 in treatment group (p=0.006). Finally, the fibrosis score was 0.7±0.48 in control group, 4,4±1.34 patient group and 3.2±0.63 in treatment group (p<0.001). There is a statistically significant positive relationship between fibrosis scores and UT-II, ET-1 and TGF-ß1 levels of an experimental lung fibrosis model.Consequently, it is thought that U-II is an important mediator in lung fibrosis model and its antagonism with palosuran could be a new treatment choice in interstitial lung fibrosis.