Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.

Abstract

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.

• Authors: Gregor Pache, Christina Schäfer, Sebastian Wiesemann, Erik Springer, Max Liebau, Hans Christian Reinhardt, Christian August, Hermann Pavenstädt, Martin Johannes Bek
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 291 Issue 3 Pg. F654-62 (Sep 2006) ISSN: 1931-857X [Print] United States
• PMID: 16622178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BMP2 protein, human
• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins
• Idb1 protein, mouse
• Inhibitor of Differentiation Protein 1
• Oligonucleotides, Antisense
• Reactive Oxygen Species
• Transforming Growth Factor beta
• NADP
• Bone Morphogenetic Protein Receptors, Type II

Topics

• Animals
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Protein Receptors, Type II (physiology)
• Bone Morphogenetic Proteins (biosynthesis)
• Humans
• Immunohistochemistry
• Inhibitor of Differentiation Protein 1 (biosynthesis, genetics)
• Kidney Glomerulus (physiology)
• Mice
• NADP (metabolism)
• Oligonucleotides, Antisense (pharmacology)
• Podocytes (physiology)
• Reactive Oxygen Species (metabolism)
• Transforming Growth Factor beta (biosynthesis)
• Up-Regulation