Synergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKD

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art_MAIRES_Synergic_Renoprotective_Effects_of_Combined_ASC_Therapy_with_2022.PDF (3.74 MB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
HINDAWI LTD
Autores
PEREIRA, Krislley R.
TELES, Flavio
BARBOSA, Paulyana F.
Citação
STEM CELLS INTERNATIONAL, v.2022, article ID 5111782, 20p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Global prevalence of chronic kidney disease (CKD) has increased considerably in the recent decades. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to renal inflammation and fibrosis, contributes to its evolution. The treatments currently employed to control CKD progression are limited and mainly based on the pharmacological inhibition of RAAS, associated with diuretics and immunosuppressive drugs. However, this conservative management promotes only partial deceleration of CKD evolution and does not completely avoid the progression of the disease and the loss of renal function, which motivates the medical and scientific community to investigate new therapeutic approaches to detain renal inflammation/fibrosis and CKD progression. Recent studies have shown the application of mesenchymal stem cells (mSC) to exert beneficial effects on the renal tissue of animals submitted to experimental models of CKD. In this context, the aim of the present study was to evaluate the effects of subcapsular application of adipose tissue-derived mSC (ASC) in rats submitted to the 5/6 renal ablation model, 15 days after the establishment of CKD, when the nephropathy was already severe. We also verify whether ASC associated to Losartan would promote greater renoprotection when compared to the respective monotherapies. Animals were followed until 30 days of CKD, when body weight, systolic blood pressure, biochemical, histological, immunohistochemical, and gene expression analysis were performed. The combination of ASC and Losartan was more effective than Losartan monotherapy in reducing systolic blood pressure and glomerulosclerosis and also promoted the complete normalization of proteinuria and albuminuria, a significant reduction in renal interstitial macrophage infiltration and downregulation of renal IL-6 gene expression. The beneficial effects of ACS are possibly due to the immunomodulatory and anti-inflammatory role of factors secreted by these cells, modulating the local immune response. Although studies are still required, our results demonstrated that a subcapsular inoculation of ASC, associated with the administration of Losartan, exerted additional renoprotective effect in rats submitted to a severe model of established CKD, when compared to Losartan monotherapy, thus suggesting ASC may be a potential adjuvant to RAAS-blockade therapy currently employed in the conservative management of CKD.
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URI
https://observatorio.fm.usp.br/handle/OPI/48286
Referências
  1. Akan E, 2021, BIOTECH HISTOCHEM, V96, P594, DOI 10.1080/10520295.2021.1875502
  2. Arias SCA, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056215
  3. Andersen S, 2010, BMC NEPHROL, V11, DOI 10.1186/1471-2369-11-29
  4. Bassi Enio Jose, 2011, World J Stem Cells, V3, P1, DOI 10.4252/wjsc.v3.i1.1
  5. Sanz AB, 2019, EXPERT REV PROTEOMIC, V16, P77, DOI 10.1080/14789450.2018.1545577
  6. Burns WC, 2010, AM J PHYSIOL-RENAL, V299, pF585, DOI 10.1152/ajprenal.00538.2009
  7. Butt L, 2020, NAT METAB, V2, P461, DOI 10.1038/s42255-020-0204-y
  8. Cavaglieri RC, 2009, TRANSPL P, V41, P947, DOI 10.1016/j.transproceed.2009.01.072
  9. Costalonga EC, 2020, STEM CELLS INT, V2020, DOI 10.1155/2020/3768718
  10. Fanelli C., 2018, CHRONIC KIDNEY DIS P, P153, DOI [10.5772/intechopen.70611, DOI 10.5772/INTECHOPEN.70611]
  11. Fanelli C, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-02915-6
  12. Fogo AB, 2003, J CLIN INVEST, V112, P326, DOI 10.1172/JCI200319375
  13. Jang HR, 2021, FRONT CELL DEV BIOL, V8, DOI 10.3389/fcell.2020.618796
  14. JEPSEN FL, 1979, VIRCHOWS ARCH A, V383, P265, DOI 10.1007/BF00430245
  15. Lambers Heerspink HJ, 2013, NAT REV NEPHROL, V9, P112, DOI 10.1038/nrneph.2012.281
  16. Liu JL, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.01843
  17. Maires M.P.C., 2021, BIORXIV, DOI [10.1101/2021.09.20.461095, DOI 10.1101/2021.09.20.461095]
  18. Mancini G, 1965, Immunochemistry, V2, P235, DOI 10.1016/0019-2791(65)90004-2
  19. MELLGREN A, 1986, DIABETOLOGIA, V29, P670, DOI 10.1007/BF00869269
  20. Noronha IL, 2002, NEPHROL DIAL TRANSPL, V17, P363, DOI 10.1093/ndt/17.3.363
  21. Noronha IL, 2011, KIDNEY INT SUPPL, V1, P77, DOI 10.1038/kisup.2011.18
  22. Ornellas FM, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-55284-7
  23. Pepineli R., 2020, J STEM CELLS RES DEV, V6, DOI [10.24966/SRDT-2060/100051, DOI 10.24966/SRDT-2060/100051]
  24. Rodriguez-Iturbe B, 2010, NEPHRON CLIN PRACT, V116, pC81, DOI 10.1159/000314656
  25. Romero C, 2015, NAT REV ENDOCRINOL, V11, P242, DOI 10.1038/nrendo.2015.6
  26. Ruster C, 2006, J AM SOC NEPHROL, V17, P2985, DOI 10.1681/ASN.2006040356
  27. Ruiz-Ortega M, 2006, NEPHROL DIAL TRANSPL, V21, P16, DOI 10.1093/ndt/gfi265
  28. Ruiz-Ortega M, 2020, NAT REV NEPHROL, V16, P269, DOI 10.1038/s41581-019-0248-y
  29. Safiri S, 2019, ANN RHEUM DIS, V78, P1463, DOI 10.1136/annrheumdis-2019-215920
  30. Saran R, 2017, AM J KIDNEY DIS, V69, DOI 10.1053/j.ajkd.2016.12.004
  31. Silva FMO, 2019, MOL MED, V25, DOI 10.1186/s10020-019-0110-5
  32. Svensson J, 2011, CELL TRANSPLANT, V20, P783, DOI 10.3727/096368910X536527
  33. Tang HJ, 2021, STEM CELL RES THER, V12, DOI 10.1186/s13287-021-02429-z
  34. WALLENSTEIN S, 1980, CIRC RES, V47, P1, DOI 10.1161/01.RES.47.1.1
  35. Wilson S, 2021, J CLIN HYPERTENS, V23, P831, DOI 10.1111/jch.14186
  36. Xing L, 2019, J CELL BIOCHEM, V120, P9737, DOI 10.1002/jcb.28254
  37. Yang Hai-Chun, 2010, Drug Discov Today Dis Models, V7, P13, DOI 10.1016/j.ddmod.2010.08.002

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/29
Artigos e Materiais de Revistas Científicas - ODS/03