Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model

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Citações na Scopus
17
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article
Data de publicação
2017
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NATURE PUBLISHING GROUP
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SCIENTIFIC REPORTS, v.7, article ID 3192, 15p, 2017
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Unidades Organizacionais
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Resumo
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1 beta and NLRP3 were individually assessed. Tlr4, Tlr5, Lbp, Nlrp3, Casp1, Irf7 and Il1b were already upregulated 15 days after Nx, while activation of Tlr2, Tlr7, Tlr9, Nod2, Tnf and Il6 was seen after 60 days post-ablation. The number of genes related to innate or adaptive immunity grew steadily with time. These observations indicate that parallel activation of innate and adaptive immunity antecedes glomerular injury and involves a growing number of intricate signaling pathways, helping to explain the difficulty in detaining renal injury in Nx as CKD advances, and, stressing the need for early treatment. Additionally, these findings may contribute to the search of therapeutic targets specific for advanced phases of CKD.
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Referências
  1. Abbas AK, 1996, NATURE, V383, P787, DOI 10.1038/383787a0
  2. Akira S, 2004, NAT REV IMMUNOL, V4, P499, DOI 10.1038/nri1391
  3. Arias SCA, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056215
  4. Anders HJ, 2007, CURR OPIN NEPHROL HY, V16, P177, DOI 10.1097/MNH.0b013e32803fb767
  5. Anders HJ, 2011, J AM SOC NEPHROL, V22, P1007, DOI 10.1681/ASN.2010080798
  6. Anders HJ, 2010, J AM SOC NEPHROL, V21, P1270, DOI 10.1681/ASN.2010030233
  7. Baroja-Mazo A, 2014, NAT IMMUNOL, V15, P738, DOI 10.1038/ni.2919
  8. Boyle JP, 2014, OPEN BIOL, V4, DOI 10.1098/rsob.140178
  9. Chang A, 2014, CURR OPIN NEPHROL HY, V23, P204, DOI 10.1097/01.mnh.0000444814.49755.90
  10. Chen EY, 2013, BMC BIOINFORMATICS, V14, DOI 10.1186/1471-2105-14-128
  11. Cheng HF, 2002, KIDNEY INT, V62, P929, DOI 10.1046/j.1523-1755.2002.00520.x
  12. Coll R. C., 2015, NATURE MED, V21
  13. Coll RC, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0029539
  14. Correa-Costa M, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0029004
  15. Costa JCSR, 2006, AM J NEPHROL, V26, P281, DOI 10.1159/000093960
  16. D'Apolito M, 2015, ATHEROSCLEROSIS, V239, P393, DOI 10.1016/j.atherosclerosis.2015.01.034
  17. Degaspari S, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0125271
  18. Donadelli R, 2000, AM J KIDNEY DIS, V36, P1226, DOI 10.1053/ajkd.2000.19838
  19. Dranoff G, 2004, NAT REV CANCER, V4, P11, DOI 10.1038/nrc1252
  20. Du PC, 2013, KIDNEY INT, V84, P265, DOI 10.1038/ki.2013.113
  21. Ekkens MJ, 2007, INFECT IMMUN, V75, P2291, DOI 10.1128/IAI.01328-06
  22. Fanelli C, 2011, AM J PHYSIOL-RENAL, V301, pF580, DOI 10.1152/ajprenal.00042.2011
  23. Finberg RW, 2004, J ENDOTOXIN RES, V10, P413, DOI 10.1179/096805104225006273
  24. FLOEGE J, 1992, LAB INVEST, V66, P485
  25. Fujihara CK, 1998, AM J PHYSIOL-RENAL, V274, pF573
  26. Fujihara CK, 2005, KIDNEY INT, V67, P1913, DOI 10.1111/j.1523-1755.2005.00290.x
  27. Fujihara CK, 2003, KIDNEY INT, V64, P2172, DOI 10.1046/j.1523-1755.2003.00319.x
  28. Fujihara CK, 1998, KIDNEY INT, V54, P1510, DOI 10.1046/j.1523-1755.1998.00138.x
  29. Fujihara CK, 2001, HYPERTENSION, V37, P170
  30. Fujihara CK, 2000, J AM SOC NEPHROL, V11, P283
  31. Fujihara CK, 2007, AM J PHYSIOL-RENAL, V292, pF92, DOI 10.1152/ajprenal.00184.2006
  32. Fujihara CK, 2010, AM J NEPHROL, V32, P95, DOI 10.1159/000315137
  33. Goncalves GM, 2011, SCAND J IMMUNOL, V73, P428, DOI 10.1111/j.1365-3083.2011.02523.x
  34. Gong W, 2016, AM J PHYSIOL-RENAL, V310, pF1081, DOI 10.1152/ajprenal.00534.2015
  35. Hsin-Yi Y., 2013, PLOS ONE, V8
  36. Hutton HL, 2016, NEPHROLOGY, V21, P736, DOI 10.1111/nep.12785
  37. Jaguin M, 2013, CELL IMMUNOL, V281, P51, DOI 10.1016/j.cellimm.2013.01.010
  38. JEPSEN FL, 1979, VIRCHOWS ARCH A, V383, P265, DOI 10.1007/BF00430245
  39. Kawai T, 2007, TRENDS MOL MED, V13, P460, DOI 10.1016/j.molmed.2007.09.002
  40. Krishnan SM, 2016, BRIT J PHARMACOL, V173, P752, DOI 10.1111/bph.13230
  41. Kuleshov M. V., 2016, NUCLEIC ACIDS RES, V8, pW90
  42. Kurts C, 2013, NAT REV IMMUNOL, V13, P738, DOI 10.1038/nri3523
  43. Lebre MC, 2005, IMMUNOL CELL BIOL, V83, P525, DOI 10.1111/j.1440-1711.2005.01365.x
  44. Leemans JC, 2014, NAT REV NEPHROL, V10, P398, DOI 10.1038/nrneph.2014.91
  45. Lehners A, 2014, AM J PHYSIOL-RENAL, V307, pF407, DOI 10.1152/ajprenal.00262.2014
  46. Lorenz G, 2014, NEPHROL DIAL TRANSPL, V29, P41, DOI 10.1093/ndt/gft332
  47. Lu KC, 2011, TOHOKU J EXP MED, V225, P109, DOI 10.1620/tjem.225.109
  48. Lu YC, 2008, CYTOKINE, V42, P145, DOI 10.1016/j.cyto.2008.01.006
  49. Machado FG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0039580
  50. Machida H, 2010, NEPHROL DIAL TRANSPL, V25, P2530, DOI 10.1093/ndt/gfq058
  51. Martino MM, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms11051
  52. Murray P. J., 2014, IMMUNITY, V41
  53. Noronha IL, 2002, NEPHROL DIAL TRANSPL, V17, P363, DOI 10.1093/ndt/17.3.363
  54. Okabe C., 2012, AM J PHYSIOL-RENAL, V15, pF155
  55. Romero F, 1999, KIDNEY INT, V55, P945, DOI 10.1046/j.1523-1755.1999.055003945.x
  56. Satirapoj B, 2012, AM J NEPHROL, V35, P520, DOI 10.1159/000338484
  57. Schroppel B, 2006, KIDNEY INT, V69, P785, DOI 10.1038/sj.ki.5000190
  58. Smith KD, 2009, CURR OPIN NEPHROL HY, V18, P189, DOI 10.1097/MNH.0b013e32832a1d5f
  59. Souza A. C. P., 2015, PHYSL REP, V3
  60. Tian S, 2015, MACROPHAGE HOUST, V2, pe679
  61. Utimura R, 2003, KIDNEY INT, V63, P209, DOI 10.1046/j.1523-1755.2003.00736.x
  62. Vilaysane A, 2010, J AM SOC NEPHROL, V21, P1732, DOI 10.1681/ASN.2010020143
  63. Zeisberg M, 2010, J AM SOC NEPHROL, V21, P1819, DOI 10.1681/ASN.2010080793