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Applications of Urinary Proteomics in Renal Disease Research Using Animal Models

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Urine Proteomics in Kidney Disease Biomarker Discovery

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 845))

Abstract

Animal models of renal disease are essential tools in research on kidney disease and have provided valuable insights into pathogenesis. Use of animal models minimises inter-individual differences, allows specific pathological changes to be examined, and facilitates collection of tissue samples. Thus, mechanistic research and identification of biomarkers are possible. Various animal models manifesting specific pathological lesions can be used to investigate acute or chronic kidney disease (CKD). Urine, a terminal metabolic product, is produced via glomerular filtration, reabsorption, and excretion in the tubular and collecting ducts, reflecting the functions of glomeruli or tubular tissue stimulated in various ways or subject to disease. Almost 70 % of urinary proteins originate from the kidney (the other 30 % come from plasma), and urinary sampling is important to noninvasively detect renal disease. Proteomics is powerful when used to screen urine components. Increasingly, urine proteomics is used to explore the pathogenesis of kidney disease in animals and to identify novel biomarkers of renal disease. In this section, we will introduce the field of urinary proteomics as applied in different models of animal renal disease and the valuable role played by proteomics in noninvasive diagnosis and rational treatment of human renal disease.

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References

  1. Akimau P, Yoshiya K, Hosotsubo H, Takakuwa T, Tanaka H, Sugimoto H (2005) New experimental model of crush injury of the hindlimbs in rats. J Trauma 58:51–58

    Article  PubMed  Google Scholar 

  2. Antoine DJ, Srivastava A, Pirmohamed M, Park BK (2010) Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells. Biochem Pharmacol 79:647–654

    Article  PubMed  CAS  Google Scholar 

  3. Blachar Y, Fong JS, de Chadarevian JP, Drummond KN (1981) Muscle extract infusion in rabbits. A new experimental model of the crush syndrome. Circ Res 49:114–124

    Article  PubMed  CAS  Google Scholar 

  4. Borza DB, Hudson BG (2003) Molecular characterization of the target antigens of anti-glomerular basement membrane antibody disease. In: Springer seminars in immunopathology, vol 24. Springer, Berlin, pp 345–361

    Google Scholar 

  5. Cui Z, Zhao MH (2011) Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol 7:697–705

    Article  PubMed  CAS  Google Scholar 

  6. Debelle FD, Nortier JL, De Prez EG, Garbar CH, Vienne AR, Salmon IJ, Deschodt-Lanckman MM, Vanherweghem JL (2002) Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol 13:431–436

    PubMed  CAS  Google Scholar 

  7. Gerth JH, Kriegsmann J, Trinh TT, Stahl RA, Wendt T, Sommer M, Stein G, Wolf G (2002) Induction of p27KIP1 after unilateral ureteral obstruction is independent of angiotensin II. Kidney Int 61:68–79

    Article  PubMed  CAS  Google Scholar 

  8. Hruska KA, Guo G, Wozniak M, Martin D, Miller S, Liapis H, Loveday K, Klahr S, Sampath TK, Morrissey J (2000) Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction. Am J Physiol Renal Physiol 279:F130–F143

    PubMed  CAS  Google Scholar 

  9. Jefferson JA, Johnson RJ (1999) Experimental mesangial proliferative glomerulonephritis (the anti-Thy-1.1 model). J Nephrol 12:297–307

    PubMed  CAS  Google Scholar 

  10. Jefferson JA, Pippin JW, Shankland SJ (2010) Experimental models of membranous nephropathy. Drug Discov Today Dis Models 7:27–33

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Kim MG, Koo TY, Yan JJ, Lee E, Han KH, Jeong JC, Ro H, Kim BS, Jo SK, Oh KH, Surh CD, Ahn C, Yang J (2013) IL-2/Anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells. J Am Soc Nephrol 24:1529–1536

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Lu Y, Liu X, Shi S, Su H, Bai X, Cai G, Yang F, Xie Z, Zhu Y, Zhang Y, Zhang S, Li X, Wang S, Wu D, Zhang L, Wu J, Xie Y, Chen X (2012) Bioinformatics analysis of proteomic profiles during the process of anti-thy1 nephritis. Mol Cell Proteomics 11:M111–008755

    Article  Google Scholar 

  13. Maddens B, Ghesquiere B, Vanholder R, Demon D, Vanmassenhove J, Gevaert K, Meyer E (2012) Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury. Mol Cell Proteomics 11:M111–013094

    Article  PubMed  PubMed Central  Google Scholar 

  14. Moreno S, Ibraghimov-Beskrovnaya O, Bukanov NO (2008) Serum and urinary biomarker signatures for rapid preclinical in vivo assessment of CDK inhibition as a therapeutic approach for PKD. Cell Cycle 7:1856–1864

    Article  PubMed  CAS  Google Scholar 

  15. Murata I, Ooi K, Sasaki H, Kimura S, Ohtake K, Ueda H, Uchida H, Yasui N, Tsutsui Y, Yoshizawa N, Hirotsu I, Morimoto Y, Kobayashi J (2011) Characterization of systemic and histologic injury after crush syndrome and intervals of reperfusion in a small animal model. J Trauma 70:1453–1463

    Article  PubMed  Google Scholar 

  16. Nabity MB, Lees GE, Dangott LJ, Cianciolo R, Suchodolski JS, Steiner JM (2011) Proteomic analysis of urine from male dogs during early stages of tubulointerstitial injury in a canine model of progressive glomerular disease. Vet Clin Pathol 40:222–236

    Article  PubMed  Google Scholar 

  17. Reynolds J (2011) Strain differences and the genetic basis of experimental autoimmune anti-glomerular basement membrane glomerulonephritis. Int J Exp Pathol 92:211–217

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rouse R, Siwy J, Mullen W, Mischak H, Metzger J, Hanig J (2012) Proteomic candidate biomarkers of drug-induced nephrotoxicity in the rat. PLoS ONE 7:e34606

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Rouse RL, Zhang J, Stewart SR, Rosenzweig BA, Espandiari P, Sadrieh NK (2011) Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int 79:1186–1197

    Article  PubMed  CAS  Google Scholar 

  20. Rucevic M, Rosenquist T, Breen L, Cao L, Clifton J, Hixson D, Josic D (2012) Proteome alterations in response to aristolochic acids in experimental animal model. J Proteomics 76:79–90

    Article  PubMed  CAS  Google Scholar 

  21. Shihab FS, Bennett WM, Tanner AM, Andoh TF (1997) Angiotensin II blockade decreases TGF-beta1 and matrix proteins in cyclosporine nephropathy. Kidney Int 52:660–673

    Article  PubMed  CAS  Google Scholar 

  22. Taal MW, Zandi-Nejad K, Weening B, Shahsafaei A, Kato S, Lee KW, Ziai F, Jiang T, Brenner BM, MacKenzie HS (2000) Proinflammatory gene expression and macrophage recruitment in the rat remnant kidney. Kidney Int 58:1664–1676

    Article  PubMed  CAS  Google Scholar 

  23. Thongboonkerd V, Klein JB, Pierce WM, Jevans AW, Arthur JM (2003) Sodium loading changes urinary protein excretion: a proteomic analysis. Am J Physiol Renal Physiol 284:F1155–F1163

    PubMed  CAS  Google Scholar 

  24. Throssell D, Brown J, Furness PN, Rutty G, Walls J, Harris KP (1997) D-penicillamine reduces renal injury in the remnant model of chronic renal failure in the rat. Nephrol Dial Transplant 12:1116–1121

    Article  PubMed  CAS  Google Scholar 

  25. Wang Y, Kramer S, Loof T, Martini S, Kron S, Kawachi H, Shimizu F, Neumayer HH, Peters H (2005) Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis. Kidney Int 68:47–61

    Article  PubMed  CAS  Google Scholar 

  26. Wang YD, Zhang L, Cai GY, Zhang XG, Lv Y, Hong Q, Shi SZ, Yin Z, Liu XF, Chen XM (2011) Fasudil ameliorates rhabdomyolysis-induced acute kidney injury via inhibition of apoptosis. Ren Fail 33:811–818

    Article  PubMed  Google Scholar 

  27. Wu L, Feng Z, Cui S, Hou K, Tang L, Zhou J, Cai G, Xie Y, Hong Q, Fu B, Chen X (2013) Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. PLoS ONE 8:e63799

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Wu T, Xie C, Bhaskarabhatla M, Yan M, Leone A, Chen SS, Zhou XJ, Putterman C, Mohan C (2007) Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance. Arthritis Rheum 56:949–959

    Article  PubMed  CAS  Google Scholar 

  29. Zhou H, Pisitkun T, Aponte A, Yuen PS, Hoffert JD, Yasuda H, Hu X, Chawla L, Shen RF, Knepper MA, Star RA (2006) Exosomal fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int 70:1847–1857

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Correspondence to Xiangmei Chen .

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Lv, Y., Cai, G., Chen, X. (2015). Applications of Urinary Proteomics in Renal Disease Research Using Animal Models. In: Gao, Y. (eds) Urine Proteomics in Kidney Disease Biomarker Discovery. Advances in Experimental Medicine and Biology, vol 845. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9523-4_14

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