Endoglin Differentially Modulates Antagonistic Transforming Growth Factor-beta1 and Bmp-7 Signaling.
From: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital, Aachen, Germany.
The Journal of biological chemistry
- Publish Date: May 2007
- ISSN: 0021-9258
- Volume: 282
- Issue: 19
- Pages: 13934-43
- Medium: Print
- Language: English
- Citation (JAMA): Scherner Olaf, Meurer Steffen K, Tihaa Lidia, et al. Endoglin Differentially Modulates Antagonistic Transforming Growth Factor-beta1 and Bmp-7 Signaling.. J. Biol. Chem. May 2007;282:13934-43
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.
Mesh Headings (Keywords): Activin Receptors, Type I, Activin Receptors, Type II, Animals, Blotting, Western, Bone Morphogenetic Proteins, COS Cells, Cell Differentiation, Cells, Cultured, Cercopithecus aethiops, Collagen Type I, Humans, Immunoprecipitation, Inhibitor of Differentiation Protein 1, Intracellular Signaling Peptides and Proteins, Liver, Luciferases, Mice, Myoblasts, Phosphorylation, Protein-Serine-Threonine Kinases, Rats, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad1 Protein, Smad2 Protein, Smad5 Protein, Transforming Growth Factor beta, Transforming Growth Factor beta1
Check for Full Text / PubMed Unique Identifier (PMID): 17376778
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