P2X7 receptor and klotho expressions in diabetic nephropathy progression

  • A. M. Rodrigues
  • R. S. Serralha
  • C. Farias
  • G. R. Punaro
  • M. J. S. Fernandes
  • Elisa Mieko Suemitsu Higa
Original Article


Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats. Diabetes was induced in Wistar rats by streptozotocin, while the control group rats received the drug vehicle. From the 1st to 8th weeks after the diabetes induction, the animals were placed in metabolic cages on the 1st day of each week for 24 h to analyze metabolic parameters and for the urine collection. Then, blood samples and the kidneys were collected for biochemical analysis, including Western blotting and qPCR for P2X7 and klotho. Diabetic rats presented a progressive loss of renal function, with reduced nitric oxide and increased lipid peroxidation. The P2X7 and klotho expressions were similar up to the 4th week; then, P2X7 expression increased in diabetes mellitus (DM), but klotho expression presented an opposite behavior, until the 8th week. Our data show an inverse correlation between P2X7 and klotho expressions through the development of DM, which suggests that the management of these molecules could be useful for controlling the progression of this disease and diabetic nephropathy.


Diabetes mellitus Oxidative stress Purinergic receptor Klotho Kidneys 



The authors acknowledge Margaret G Mouro and Deyse Y Lima for their technical assistance and Professor Sergio R R Araujo for the histological analysis. This study was supported by Coordenaçao de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundaçao de Apoio a Pesquisa da UNIFESP (FAP).

Compliance with ethical standards

Conflicts of interest

A. M. Rodrigues declares that he has no conflict of interest.

R. S. Serralha declares that he has no conflict of interest.

C. Farias declares that she has no conflict of interest.

G. R. Punaro declares that she has no conflict of interest.

M. J. S. Fernandes declares that she has no conflict of interest.

Elisa Mieko Suemitsu Higa declares that she has no conflict of interest.

Ethical approval

The protocol was approved by the Ethics Committee in Research of Universidade Federal de Sao Paulo under protocol #2056100314.


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • A. M. Rodrigues
    • 1
    • 2
  • R. S. Serralha
    • 2
    • 3
  • C. Farias
    • 2
    • 3
  • G. R. Punaro
    • 2
    • 3
  • M. J. S. Fernandes
    • 4
  • Elisa Mieko Suemitsu Higa
    • 1
    • 2
    • 3
    • 5
  1. 1.Translational MedicineUniversidade Federal de Sao PauloSao PauloBrazil
  2. 2.Laboratory of Nitric Oxide and Oxidative StressUniversidade Federal de Sao PauloSao PauloBrazil
  3. 3.NephrologyUniversidade Federal de Sao PauloSao PauloBrazil
  4. 4.Neurology and NeurosurgeryUniversidade Federal de Sao PauloSao PauloBrazil
  5. 5.Department of MedicineUniversidade Federal de Sao PauloSao PauloBrazil

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