Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury

Carregando...
Imagem de Miniatura
Citações na Scopus
39
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
Citação
PHYSIOLOGICAL REPORTS, v.4, n.13, article ID e12829, 13p, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI. We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI. Wistar rats were fed vitamin D-free or standard diets for 35days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI. Indices of renal injury and recovery were evaluated for up to 7days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.
Palavras-chave
Acute kidney injury, CD4(+) lymphocytes, CD8(+) lymphocytes, cytokines, ischemia reperfusion injury, renal microvascular density, T-reg cells, vitamin D deficiency
Referências
  1. Ascon DB, 2008, J LEUKOCYTE BIOL, V84, P1400, DOI 10.1189/jlb.0907651
  2. Ascon M, 2009, KIDNEY INT, V75, P526, DOI 10.1038/ki.2008.602
  3. Basile DP, 2007, KIDNEY INT, V72, P151, DOI 10.1038/sj.ki.5002312
  4. Basile DP, 2011, AM J PHYSIOL-RENAL, V300, pF721, DOI 10.1152/ajprenal.00546.2010
  5. Basile David P., 2014, Cardiovascular & Hematological Disorders - Drug Targets, V14, P3
  6. Basile DP, 2016, J AM SOC NEPHROL, V27, P687, DOI 10.1681/ASN.2015030309
  7. Basile DP, 2008, AM J PHYSIOL-RENAL, V294, pF928, DOI 10.1152/ajprenal.00596.2007
  8. Basile DP, 2001, AM J PHYSIOL-RENAL, V281, pF887
  9. Belayev LY, 2014, CURR OPIN NEPHROL HY, V23, P149, DOI 10.1097/01.mnh.0000441051.36783.f3
  10. Braun Andrea B., 2013, Inflammation & Allergy Drug Targets, V12, P262
  11. Braun AB, 2012, CRIT CARE MED, V40, P3170, DOI 10.1097/CCM.0b013e318260c928
  12. Burne MJ, 2001, J CLIN INVEST, V108, P1283, DOI 10.1172/JCI12080
  13. Charron AJ, 1999, AM J PHYSIOL-HEART C, V277, pH1985
  14. Chawla LS, 2011, KIDNEY INT, V79, P1361, DOI 10.1038/ki.2011.42
  15. Chawla LS, 2012, KIDNEY INT, V82, P516, DOI 10.1038/ki.2012.208
  16. Choi HY, 2015, STEM CELL RES THER, V6, DOI 10.1186/s13287-015-0012-6
  17. Coca SG, 2012, KIDNEY INT, V81, P442, DOI 10.1038/ki.2011.379
  18. Day YJ, 2006, J IMMUNOL, V176, P3108
  19. desAraujo M., 2005, J AM SOC NEPHROL, V16, P3339
  20. desBoer I. H., 2011, CLIN J AM SOC NEPHRO, V6, P2141
  21. desBraganca A. C., 2015, PHYSL REP, V3
  22. Dusso AS, 2012, KIDNEY INT, V81, P937, DOI 10.1038/ki.2012.30
  23. Dusso AS, 2005, AM J PHYSIOL-RENAL, V289, pF8, DOI 10.1152/ajprenal.00336.2004
  24. Gandolfo MT, 2009, KIDNEY INT, V76, P717, DOI 10.1038/ki.2009.259
  25. Goncalves JG, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0107228
  26. Jang HR, 2009, J MOL MED-JMM, V87, P859, DOI 10.1007/s00109-009-0491-y
  27. Jang HR, 2009, CLIN IMMUNOL, V130, P41, DOI 10.1016/j.clim.2008.08.016
  28. Kienreich K, 2013, NUTRIENTS, V5, P3005, DOI 10.3390/nu5083005
  29. Kramann R, 2014, J AM SOC NEPHROL, V25, P1924, DOI 10.1681/ASN.2013101121
  30. Lancas T, 2011, RESPIRATION, V82, P177, DOI 10.1159/000326897
  31. Lanske B, 2007, J NUTR BIOCHEM, V18, P771, DOI 10.1016/j.jnutbio.2007.02.002
  32. Liang M, 2015, KIDNEY INT, V88, P490, DOI 10.1038/ki.2015.73
  33. Manickam N, 2014, AM J PHYSIOL-RENAL, V307, pF159, DOI 10.1152/ajprenal.00546.2013
  34. Megyesi J, 1996, AM J PHYSIOL-RENAL, V271, pF1211
  35. Mehrotra P, 2015, KIDNEY INT, V88, P776, DOI 10.1038/ki.2015.200
  36. Miyaji T, 2001, J AM SOC NEPHROL, V12, P900
  37. Moe SM, 2008, PRIMARY CARE, V35, P215, DOI 10.1016/j.pop.2008.01.007
  38. Molinari C, 2011, CELL PHYSIOL BIOCHEM, V27, P661, DOI 10.1159/000330075
  39. Patel TV, 2009, SEMIN NEPHROL, V29, P113, DOI 10.1016/j.semnephrol.2009.01.004
  40. Rabb H, 2000, AM J PHYSIOL-RENAL, V279, pF525
  41. Venkatachalam MA, 2010, AM J PHYSIOL-RENAL, V298, pF1078, DOI 10.1152/ajprenal.00017.2010
  42. Wu VC, 2014, J AM HEART ASSOC, V3, DOI 10.1161/JAHA.114.000933
  43. Zhou LL, 2015, J AM SOC NEPHROL, V26, P677, DOI 10.1681/ASN.2013101067