• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2018.tde-31012018-140525
Document
Author
Full name
Marina Barguil Macêdo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Festuccia, William Tadeu Lara
Fujihara, Clarice Kazue
Volpini, Rildo Aparecido
Title in Portuguese
Papel protetor da quinase ativada por adenosina monofosfato (AMPK) na progressão e severidade da nefrite tubulointersticial experimental.
Keywords in Portuguese
Doença renal crônica
Imunometabolismo
Macrófagos
Metformina
Quinase ativada por adenosina monofosfato (AMPK)
Abstract in Portuguese
Objetivamos investigar o papel da quinase ativada por adenosina monofosfato (AMPK) na doença renal crônica. Induzimos nefrite túbulo-intersticial (NTI) em camundongos C57BL/6 e LyzM-cre AMPKflox/flox através de ração com adenina, e tratamos com metformina (Met) 200 mg/kg/dia. Avaliamos ainda o efeito da Met sobre a transição epitélio-mesenquimal (TEM) em células tubulares epiteliais renais murinas (linhagem MM55.K). Os C57BL/6 tratados apresentaram preservação da função renal; maior frequência de macrófagos (MØ) M1, em detrimento dos M2; e redução de marcadores de fibrose. Os LyzM-cre AMPK-/- não diferiram dos LyzM-cre AMPK+/+ quanto à intensidade da lesão, por a molécula já se encontrar infrarregulada na NTI. Contudo, ao serem tratados com Met, os LyzM-cre AMPK+/+ evoluíram melhor do que os não tratados, o mesmo não se verificando nos LyzM-cre AMPK-/-, sugerindo que a ação da Met nos MØ é dependente de AMPK. As MM55.K, após estímulo com Met, exibiram maior captação de glicose, expressão do transportador Glut-2, ativação da glicólise, e resistência à TEM.
Title in English
Protective role of adenosine monophosphate activated kinase (AMPK) on the progression and severity of experimental tubulointerstitial nephritis.
Keywords in English
Adenosine monophosphate activated kinase (AMPK)
Chronic kidney disease
Immunometabolism
Macrophages
Metformin
Abstract in English
We aimed to investigate the role of adenosine monophosphate activated kinase (AMPK) on chronic kidney disease. We induced tubulointerstitial nephritis (TIN) in C57BL/6 and LyzM-cre AMPKflox/flox mice by feeding them adenine diet, and then treating with metformin (Met) 200 mg/kg/day. We also evaluated the effect of Met on epithelium-to-mesenchyma transition (EMT) of murine epithelial renal tubular cells (lineage MM55.K). Met-treated C57BL/6 mice presented preserved kidney function, greater frequency of M1 macrophages (MØ) compared to M2 ones, and reduced markers of fibrosis. Disease severity on LyzM-cre AMPK-/- and AMPK+/+ mice did not differ, since the molecule was already downregulated on TIN. However, by treating them with Met, LyzM-cre AMPK+/+ improved in comparison to the non-treated mice. The same did not happen with LyzM-cre AMPK-/- mice, suggesting that Met effect on MØ is AMPK-dependent. MM55.K cells, after stimulus with Met, showed increased glucose uptake, greater expression of the transporter Glut-2, activation of glycolysis, and resistance to EMT.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Release Date
2020-01-31
Publishing Date
2018-01-31
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2021. All rights reserved.