Urinary Sediment Transcriptomic and Longitudinal Data to Investigate Renal Function Decline in Type 1 Diabetes

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Citações na Scopus
5
Tipo de produção
article
Data de publicação
2020
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Citação
FRONTIERS IN ENDOCRINOLOGY, v.11, article ID 238, 8p, 2020
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Introduction: Using a discovery/validation approach we investigated associations between a panel of genes selected from a transcriptomic study and the estimated glomerular filtration rate (eGFR) decline across time in a cohort of type 1 diabetes (T1D) patients. Experimental: Urinary sediment transcriptomic was performed to select highly modulated genes in T1D patients with rapid eGFR decline (decliners) vs. patients with stable eGFR (non-decliners). The selected genes were validated in samples from a T1D cohort (n = 54, mean diabetes duration of 21 years, 61% women) followed longitudinally for a median of 12 years in a Diabetes Outpatient Clinic. Results: In the discovery phase, the transcriptomic study revealed 158 genes significantly different between decliners and non-decliners. Ten genes increasingly up or down-regulated according to renal function worsening were selected for validation by qRT-PCR; the genes CYP4F22, and PMP22 were confirmed as differentially expressed comparing decliners vs. non-decliners after adjustment for potential confounders. CYP4F22, LYPD3, PMP22, MAP1LC3C, HS3ST2, GPNMB, CDH6, and PKD2L1 significantly modified the slope of eGFR in T1D patients across time. Conclusions: Eight genes identified as differentially expressed in the urinary sediment of T1D patients presenting different eGFR decline rates significantly increased the accuracy of predicted renal function across time in the studied cohort. These genes may be a promising way of unveiling novel mechanisms associated with diabetic kidney disease progression.
Palavras-chave
diabetic kidney disease, transcriptomics, renal function decline, longitudinal data, type 1 diabetes, urine
Referências
  1. Chen Z, 2016, BMC NEPHROL, V17, DOI 10.1186/s12882-016-0366-8
  2. Colhoun HM, 2018, DIABETOLOGIA, V61, P996, DOI 10.1007/s00125-018-4567-5
  3. Conway BR, 2012, KIDNEY INT, V82, P812, DOI 10.1038/ki.2012.218
  4. DeFronzo R, 2015, INT TXB DIABETES MEL, V2
  5. DeLuca DS, 2012, BIOINFORMATICS, V28, P1530, DOI 10.1093/bioinformatics/bts196
  6. Dobin A, 2013, BIOINFORMATICS, V29, P15, DOI 10.1093/bioinformatics/bts635
  7. Du J, 2015, J BIOL CHEM, V290, P12000, DOI 10.1074/jbc.M115.636969
  8. George NI, 2014, BMC BIOINFORMATICS, V15, DOI 10.1186/1471-2105-15-92
  9. Harder JL, 2019, JCI INSIGHT, V4, DOI 10.1172/jci.insight.122697
  10. Hills CE, 2011, CYTOKINE GROWTH F R, V22, P131, DOI 10.1016/j.cytogfr.2011.06.002
  11. Hoopes SL, 2015, PROSTAG OTH LIPID M, V120, P9, DOI 10.1016/j.prostaglandins.2015.03.002
  12. Lepedda AJ, 2017, J DIABETES COMPLICAT, V31, P149, DOI 10.1016/j.jdiacomp.2016.10.013
  13. Kalsotra A, 2005, BIOCHEM BIOPH RES CO, V338, P423, DOI 10.1016/j.bbrc.2005.08.101
  14. Koukourakis MI, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0137675
  15. Levey AS, 2009, ANN INTERN MED, V150, P604, DOI 10.7326/0003-4819-150-9-200905050-00006
  16. Li B, 2010, FASEB J, V24, P4767, DOI 10.1096/fj.10-154757
  17. Liao Y, 2014, BIOINFORMATICS, V30, P923, DOI 10.1093/bioinformatics/btt656
  18. Liu H, 2008, J AM SOC NEPHROL, V19, P714, DOI 10.1681/ASN.2007060713
  19. Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262
  20. Matboli M, 2017, J DIABETES COMPLICAT, V31, P1491, DOI 10.1016/j.jdiacomp.2017.06.009
  21. McGiff JC, 1999, AM J PHYSIOL-REG I, V277, pR607
  22. Monteiro MB, 2016, METABOLISM, V65, P816, DOI 10.1016/j.metabol.2016.02.012
  23. Monteiro MB, 2016, FREE RADICAL RES, V50, P101, DOI 10.3109/10715762.2015.1109083
  24. Mortazavi A, 2008, NAT METHODS, V5, P621, DOI 10.1038/nmeth.1226
  25. Muroya Y, 2015, J AM SOC NEPHROL, V26, P2460, DOI 10.1681/ASN.2014090868
  26. Ohno Y, 2015, P NATL ACAD SCI USA, V112, P7707, DOI 10.1073/pnas.1503491112
  27. Parsa A, 2017, J AM SOC NEPHROL, V28, P923, DOI 10.1681/ASN.2015101152
  28. Patel-Chamberlin M, 2011, KIDNEY INT, V79, P1138, DOI 10.1038/ki.2011.28
  29. Plaisier E, 2005, J AM SOC NEPHROL, V16, P3350, DOI 10.1681/ASN.2005050509
  30. Roman RJ, 2002, PHYSIOL REV, V82, P131, DOI 10.1152/physrev.00021.2001
  31. Roux KJ, 2005, MOL BIOL CELL, V16, P1142, DOI 10.1091/mbc.E04-07-0551
  32. Simpson AECM, 1997, GEN PHARMACOL-VASC S, V28, P351, DOI 10.1016/S0306-3623(96)00246-7
  33. Tesch GH, 2010, NEPHROLOGY, V15, P609, DOI 10.1111/j.1440-1797.2010.01361.x
  34. Teumer A, 2016, DIABETES, V65, P803, DOI 10.2337/db15-1313
  35. Tiwari P, 2018, ADV EXP MED BIOL, V1112, P107, DOI 10.1007/978-981-13-3065-0_9
  36. Wang J, 2017, NUCLEIC ACIDS RES, V45, pW130, DOI 10.1093/nar/gkx356
  37. Yang DY, 2018, CELL MOL LIFE SCI, V75, P669, DOI 10.1007/s00018-017-2639-1
  38. Zoltewicz SJ, 2012, ASN NEURO, V4, DOI 10.1042/AN20120045