Effects Of Protease Activated Receptor (PAR)2 Blocking Peptide On Endothelin-1 Levels In Kidney Tissues In Endotoxemic Rat Model

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dr.. Chishimba Nathan Mowa, Associate Professor (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

Abstract: Aims: Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-a in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-a levels.Main methods: Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10 h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3 h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. Key fndings: An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-a peaked (around 12-fold) at 1 h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-a levels.Significance: The present study reveals a distinct chronological expression of ET-1 and TNF-a in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.

Additional Information

Publication
Chishimba Nathan Mowa, Subrina Jesmin, Nobutake Shimojo, Naoto Yamaguchi, Masami Oki,Sohel Zaedi, Sayeeda Nusrat Sultana, Arifur Rahman, Majedul Islam, Atsushi Sawamura,Satoshi Gando, Satoru Kawano, Takashi Miyauchi & Taro Mizutani (2014) "Effects Of Protease Activated Receptor (PAR)2 Blocking Peptide On Endothelin-1 Levels In Kidney Tissues In Endotoxemic Rat Model" Life Sciences #102 pp.127-133. Version of Record Available From www.sciencedirect.com
Language: English
Date: 2014
Keywords
Lipopolysaccharide, Kidney, Protease activated receptor 2, Endothelin-1, Tumor necrosis factor-a

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