Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.
Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a major role in kidney development and disease. Here, we show the existence 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 Ca(2+) 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.
Pache
Gregor
G
Department of Medicine, Division of Nephrology and General Medicine, University Clinic of Freiburg, Freiburg, Germany.
Schäfer
Christina
C
Wiesemann
Sebastian
S
Springer
Erik
E
Liebau
Max
M
Reinhardt
Hans Christian
HC
August
Christian
C
Pavenstädt
Hermann
H
Bek
Martin Johannes
MJ
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D007678:Kidney Glomerulus / Q000502:physiology; D051379:Mice; D009249:NADP / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D050199:Podocytes / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D016376:Oligonucleotides, Antisense; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D009249:NADP; D052006:Bone Morphogenetic Protein Receptors, Type II