title: Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.
abstract: OBJECTIVE
  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)-α 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-α levels.
  
  
  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 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney.
  
  
  RESULTS
  An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels.
  
  
  CONCLUSIONS
  The present study reveals a distinct chronological expression of ET-1 and TNF-α 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.
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh; Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan. Electronic address: jsubrina@gmail.com.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: nokeshimojo@yahoo.co.jp.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Shimojo
authors.affiliation: Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan. Electronic address: yamaguchi@ipu.ac.jp.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Department of Biology, Appalachian State University, NC, USA. Electronic address: mowacn@appstate.edu.
authors.forename: Chishimba Nathan
authors.initials: CN
authors.lastname: Mowa
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: s1321258@u.tsukuba.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Oki
authors.affiliation: Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh; Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan. Electronic address: zaedi0728@yahoo.com.
authors.forename: Sohel
authors.initials: S
authors.lastname: Zaedi
authors.affiliation: Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh.
authors.forename: Sayeeda Nusrat
authors.initials: SN
authors.lastname: Sultana
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh. Electronic address: rarif111@yahoo.com.
authors.forename: Arifur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh. Electronic address: majedul1987@yahoo.com.
authors.forename: Majedul
authors.initials: M
authors.lastname: Islam
authors.affiliation: Department of Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawamura
authors.affiliation: Department of Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: Gando@med.hokudai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: kawano_s@md.tsukuba.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: t-miyauc@md.tsukuba.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: mizutani@md.tsukuba.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Mizutani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D044464:Receptor, PAR-2; D014409:Tumor Necrosis Factor-alpha
keywords: Endothelin-1; Kidney; Lipopolysaccharide; Protease activated receptor 2; Tumor necrosis factor-α