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| Damage effect of extracellular histones on renal tubular cells and the relating mechanism |
| ZHU Qifan, WANG Dexuan, CHEN Xinxin, ZHUANG Jieqiu, CAI Hui. |
Department of Pediatrics Nephrology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027
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| Cite this article: |
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ZHU Qifan,WANG Dexuan,CHEN Xinxin, et al. Damage effect of extracellular histones on renal tubular cells and the relating mechanism [J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2017, 47(5): 325-328.
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Abstract Objective: To explore the damage effect of extracellular histones on the renal tubular cells (Cos-7 cell) and the relating mechanism. Methods: Cos-7 cells stimulated by different concentration (0, 50, 100, 200 μg/mL) of histones were observed. After treatment with histones (100 μg/mL), Cos-7 cells were collected to detect the expression of T-cell immunoglobulin and mucindomain-containing molecules-1 (TIM1), cysteine aspartate-specific protease 3 (caspase3) and Toll-like receptor-2 (TLR-2) by Western blot at different time points (0, 12, 24, and 48 h). Results: The activity of the Cos-7 cells decreased with the increase of histones concentration. Under the same histones concentration, the expression of TIM1, cleaved-caspase3/t-caspase3 and TLR-2 increased with the stimulation time of the histones. Conclusion: Extracelluar histones induce the kidney injury, and the mechanism may be the induction of renal tubular cell apoptosis through TLR-2 signaling pathway.
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Received: 05 December 2016
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[1] XU J, ZHANG X, PELAYO R, et al. Extracellular histones are major mediators of death in sepsis[J]. Nat Med, 2009, 15(11): 1318-1321.
[2] ALLAM R, SCHERBAUM C R, DARISIPUDI M N, et al. Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4[J]. J Am Soc Nephrol, 2012, 23(8): 1375-1388.
[3] JOHANSSON P I, WINDELøV N A, RASMUSSEN L S,
et al. Blood levels of histone-complexed DNA fragments are associated with coagulopathy, inflammation and endothelial damage early after trauma[J]. J Emerg Trauma Shock, 2013, 6(3): 171-175.
[4] ALLAM R, KUMAR S V, DARISIPUDI M N, et al. Extra-cellular histones in tissue injury and inflammation[J]. Mol Med, 2014, 92(5): 465-472.
[5] ABRAMS S T, ZHANG N, MANSON J, et al. Circulating histones are mediators of trauma-associated lung injury[J]. Am J Respir Crit Care Med, 2013, 187(2): 160-169.
[6] ZHANG H, VILLAR J, SLUTSKY A S. Circulating histones: a novel target in acute respiratory distress syndrome [J]. Am J Respir Crit Care Med, 2013, 187(2): 118-120.
[7] BAILLY V, ZHANG Z, MEIER W, et al. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration[J]. J Biol Chem, 2002, 277(42): 39739-39748.
[8] HUANG H, EVANKOVICH J, YAN W, et al. Endogenous histones function as alarmins in sterile inflammatory liver injury through toll-like receptor 9 in mice[J]. Hepatology, 2011, 54(3): 999-1008.
[9] XU J, ZHANG X, MONESTIER M, et al. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fetal liver injury[J]. J Immunol, 2011, 187(5): 2626-2631.
[10] WEN Z, LIU Y, LI F, et al. Circulating histones exacerbates inflammation in mice with acute liver failure[J]. J Cell Biochem, 2013, 114(10): 2384-2391.
[11] FRIGGER A, BANER J S, XIE N, et al. Extracellular histones inhibit efferocytosis[J]. Mol Med, 2012, 18(1): 825-833.
[12] EKANEV M L, OTTO G P, SOSSDORF M, et al. Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation[J]. Crit Care, 2014, 18(5):543.
[13] BANNISTER A J, KOUZARIDES T. Regulation of chromatin by histone modifications[J]. Cell Res, 2011, 21(3): 381-395.
[14] KLEIN B, LüTZ-MEINDL U, KERSCHBAUM H H. From the nucleus to the plasma membrane: translocation of the nuclear proteins histone H3 and lamin B1 in apoptotic microglia[J]. Apoptosis, 2014, 19(5): 759-775.
[15] 卿吉琳, 赵林, 赵仁峰, 等. TIM基因家族在疾病中作用的研究进展[J]. 中国免疫学杂志, 2015, 31(4): 573-576.
[16] HAN W K, BAILLY V, ABICHANDANI R, et al. Kidney injury molecule-1 (kim-1): A novel biomarker for human renal proximal tubule injury[J]. Kidney Int, 2002, 62(1): 237-244.
[17] REDDI A H. Inhibition of cell death in the intervertebral disc by caspase 3 small interfering RNA[J]. Arthritis Rheum, 2011, 63(6): 1477-1478.
[18] HENRICK B M, YAO X D, TAHA A Y, et al. Insights into soluble Toll-like receptor 2 as a downregulator of virally induced inflammation[J]. Front Immunol, 2016, 7: 291.
[19] ZHANG Q, RAOOF M, CHEN Y, et al. Circulating mito-chondrial DAMPs cause inflammatory responses to injury [J]. Nature, 2010, 464(7285): 104-107. |
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