Urotensin receptors as a new target for CLP induced septic lung injury in mice
Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1β, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1β, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.
KeywordsLung damage Palosuran Sepsis Urantide Urotensin Urotensin receptor
EC, ZH, and EA conceived and designed research and conducted the experiment. EC, BD, and AG wrote the manuscript. BG performed the histopathological analyses. IC and EC analyzed the data. All authors read and approved the manuscript.
This study was supported by Turkish Academy of Sciences (TUBA)—The Young Scientist Award Program (GEBIP) with project number “EC/TUBAGEBIP-20135.”
Compliance with ethical standards
Animal experiments and procedures were performed by the national guidelines for the use and care of laboratory animals and approved by Ataturk University’s local animal care committee.
Conflict of interest
The authors declare that they have no conflict of interest.
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