Subrina Jesmin1, Nobutake Shimojo2, Naoto Yamaguchi3, Chishimba Nathan Mowa4, Masami Oki5, Sohel Zaedi6, Sayeeda Nusrat Sultana7, Arifur Rahman8, Majedul Islam9, Atsushi Sawamura10, Satoshi Gando11, Satoru Kawano12, Takashi Miyauchi13, Taro Mizutani14. 1. 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. 2. Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: nokeshimojo@yahoo.co.jp. 3. Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan. Electronic address: yamaguchi@ipu.ac.jp. 4. Department of Biology, Appalachian State University, NC, USA. Electronic address: mowacn@appstate.edu. 5. Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: s1321258@u.tsukuba.ac.jp. 6. 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. 7. Health and Disease Research Center for Rural Peoples, Dhaka, Bangladesh. 8. 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. 9. 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. 10. Department of Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 11. Department of Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: Gando@med.hokudai.ac.jp. 12. Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: kawano_s@md.tsukuba.ac.jp. 13. Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: t-miyauc@md.tsukuba.ac.jp. 14. Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: mizutani@md.tsukuba.ac.jp.
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)-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. 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 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
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)-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. 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 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. KEY FINDINGS: 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. SIGNIFICANCE: 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: Casey M Rebholz; Jane L Harman; Morgan E Grams; Adolfo Correa; Daichi Shimbo; Josef Coresh; Bessie A Young Journal: J Am Soc Nephrol Date: 2017-07-11 Impact factor: 10.121
Authors: Carmen De Miguel; Joshua S Speed; Malgorzata Kasztan; Eman Y Gohar; David M Pollock Journal: Curr Opin Nephrol Hypertens Date: 2016-01 Impact factor: 2.894
Authors: Carmen De Miguel; William C Hamrick; Janet L Hobbs; David M Pollock; Pamela K Carmines; Jennifer S Pollock Journal: Sci Rep Date: 2017-02-23 Impact factor: 4.379