Submitted on June 8, 2004
Accepted on March 29, 2006
Up-regulation of Id-1 via BMP-2 Receptors Induces
Reactive Oxygen Species in Podocytes
Gregor Pache1, Christina Schafer2, Sebastian Wiesemann1, Erik Springer2, Max Liebau1, Hans Christian Reinhardt3, Christian August4, Hermann Pavenstadt5*, and Martin J Bek2
1 Nephrology, University Clinic of Freiburg, Freiburg, Germany
2 Nephrology, University Clinic of Muenster, Muenster, Germany
3 Nephrology, University Clinic of Munster, United States
4 Pathology, University Clinic of Muenster, Muenster, Germany
5 Nephrology, University Clinic of Muenster, United States
* To whom correspondence should be addressed. E-mail: Hermann.Pavenstaedt{at}ukmuenster.de.
Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a major role in kidney development and disease. Here we show the existance of mRNA for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2 and ACVR2B in differentiated mouse podocytes and the protein expression of BMPR1A in human glomerular podocytes. BMP-2 dose-dependently increases the free cytosolic Ca2+ concentration in podocytes proving the existence of a functional receptor in these cells. Recent data indicate, that in a myoblastic cell line and in a breast cancer cell line BMP-2 increases the expression of Id-1, a negative regulator of basic helix-loop-helix transcription factors, but the role of BMP-2 stimulated Id-1 expression in the kidney has not been further characterized. Here we show, that BMP-2 increases the expression of Id-1 in differentiated podocytes. To investigate a role of Id-1 for podocyte function overexpression of Id-1 was induced in differentiated mouse podocytes. Id-1 overexpressing podocytes show an increased NADPH dependent production of reactive oxygen species (ROS). This effect can be evoked by BMP-2 and can be antagonized by anti-Id-1 antisense oligonucleotides. The data indicate that BMP-2 may - via an increased expression of Id-1 and an increased generation of ROS - contribute to important cellular functions in podocytes. ROS supposedly play a major role in cell adhesion, cell injury, ion transport, fibrogenesis, angiogenesis and are involved in the pathogenesis of membranous nephropathy.
