Abstract |
Transforming growth factor-beta1 (TGF-beta1) and BMP-7 ( bone morphogenetic protein-7; OP-1) play central, antagonistic roles in kidney fibrosis, a setting in which the expression of endoglin (CD105), an accessory TGF-beta type III receptor, is increased. So far, endoglin is known as a negative regulator of TGF-beta/ALK-5 signaling. Here we analyzed the effect of BMP-7 on TGF-beta1 signaling and the role of endoglin for both pathways in endoglin-deficient L(6)E(9) cells. In this myoblastic cell line, TGF-beta1 and BMPs are opposing cytokines, interfering with myogenic differentiation. Both induce specific target genes of which Id1 (for BMPs) and collagen I (for TGF-beta1) are two examples. TGF-beta1 activated two distinct type I receptors, ALK-5 and ALK-1, in these cells. Although the ALK-5/Smad3 signaling pathway mediated collagen I expression, ALK-1/Smad1/Smad5 signaling mediated a transient Id1 up-regulation. In contrast, BMP-7 exclusively activated Smad1/Smad5 resulting in a more prolonged Id1 expression. Although BMP-7 had no impact on collagen I abundance, it antagonized TGF-beta1-induced collagen I expression and (CAGA)(12)-MLP-Luc activity, effects that are mediated by the ALK-5/Smad3 pathway. Finally, we found that the transient overexpression of endoglin, previously shown to inhibit TGF-beta1-induced ALK-5/Smad3 signaling, enhanced the BMP-7/Smad1/Smad5 pathway.
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Authors | Olaf Scherner, Steffen K Meurer, Lidia Tihaa, Axel M Gressner, Ralf Weiskirchen |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 282
Issue 19
Pg. 13934-43
(May 11 2007)
ISSN: 0021-9258 [Print] United States |
PMID | 17376778
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BMP7 protein, human
- Bmp7 protein, rat
- Bone Morphogenetic Protein 7
- Bone Morphogenetic Proteins
- Collagen Type I
- Endoglin
- Eng protein, rat
- Idb1 protein, mouse
- Inhibitor of Differentiation Protein 1
- Intracellular Signaling Peptides and Proteins
- Receptors, Transforming Growth Factor beta
- Smad1 Protein
- Smad1 protein, rat
- Smad2 Protein
- Smad2 protein, rat
- Smad5 Protein
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Luciferases
- Protein Serine-Threonine Kinases
- ACVRL1 protein, human
- Activin Receptors, Type I
- Activin Receptors, Type II
- Receptor, Transforming Growth Factor-beta Type I
- TGFBR1 protein, human
- Tgfbr1 protein, mouse
- Tgfbr1 protein, rat
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Topics |
- Activin Receptors, Type I
(metabolism)
- Activin Receptors, Type II
(metabolism)
- Animals
- Blotting, Western
- Bone Morphogenetic Protein 7
- Bone Morphogenetic Proteins
(metabolism)
- COS Cells
- Cell Differentiation
- Cells, Cultured
- Chlorocebus aethiops
- Collagen Type I
(metabolism)
- Endoglin
- Humans
- Immunoprecipitation
- Inhibitor of Differentiation Protein 1
(metabolism)
- Intracellular Signaling Peptides and Proteins
(pharmacology)
- Liver
(cytology, metabolism)
- Luciferases
- Mice
- Myoblasts
(cytology, metabolism)
- Phosphorylation
- Protein Serine-Threonine Kinases
- Rats
- Receptor, Transforming Growth Factor-beta Type I
- Receptors, Transforming Growth Factor beta
(metabolism)
- Signal Transduction
- Smad1 Protein
(metabolism)
- Smad2 Protein
(metabolism)
- Smad5 Protein
(metabolism)
- Transforming Growth Factor beta
(metabolism)
- Transforming Growth Factor beta1
(antagonists & inhibitors, metabolism)
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