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P2Y-receptors stimulating the proliferation of human mesangial cells through the MAPK42/44 pathway

Oliver Vonend1, Tobias Grote, Vitus Oberhauser

  • 1Department of Internal Medicine, Marienhospital Herne, Ruhr-University Bochum, Germany.

British Journal of Pharmacology
|July 23, 2003
PubMed

Insights

Adenosine triphosphate (ATP) stimulates human mesangial cell proliferation and DNA synthesis by activating the MAPK pathway. ATP also enhances platelet-derived growth factor-induced cell hyperplasia in kidney cells.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Biology

Background:

  • Mesangial cell proliferation is a hallmark of various kidney diseases.
  • Adenosine triphosphate (ATP), a sympathetic cotransmitter, is implicated in proliferative processes.

Purpose of the Study:

  • To investigate the effects of exogenous ATP on human mesangial cells in culture.
  • To determine the role of ATP in cell proliferation and DNA synthesis.

Main Methods:

  • Human mesangial cells were cultured from kidney cortex.
  • Assessed nucleotide effects on [(3)H]thymidine incorporation, MAPK activation, and cell number.
  • Characterized P2-receptors pharmacologically and by RT-PCR for P2Y and P2X subtypes.

Main Results:

  • ATP and ADP significantly increased [(3)H]thymidine incorporation (up to 220%).
  • ATP activated the MAPK(42/44) pathway, which was inhibited by PD 98059.
  • ATP amplified platelet-derived growth factor (PDGF)-induced cell proliferation.

Conclusions:

  • ATP exhibits mitogenic effects on human mesangial cells.
  • ATP-induced DNA synthesis involves MAPK(42/44) pathway activation.
  • ATP potentiates PDGF-stimulated mesangial cell hyperplasia.

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