Distinct bone morphogenetic proteins activate indistinguishable transcriptional responses in nephron epithelia including Notch target genes
| Autor: | Leif Oxburgh, Barry W. Larman, Michele J. Karolak, Volkhard Lindner |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
animal structures Transcription Genetic Cell Cycle Proteins Nerve Tissue Proteins Smad Proteins SMAD Nephron Biology Bone morphogenetic protein Bone morphogenetic protein 2 Article Cell Line Kidney Tubules Proximal Mice Genes Reporter Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans Phosphorylation Eye Proteins Promoter Regions Genetic HEY1 Luciferases Renilla Receptors Notch Gene Expression Profiling Bone morphogenetic protein 10 Epithelial Cells Cell Biology Molecular biology Recombinant Proteins Cell biology BMPR2 Bone morphogenetic protein 7 medicine.anatomical_structure Bone Morphogenetic Proteins embryonic structures |
| Zdroj: | Cellular Signalling. 24:257-264 |
| ISSN: | 0898-6568 |
| Popis: | Endogenous Bone Morphogenetic Protein (BMP) signaling plays a significant role in the kidney's recovery from acute injury and exogenous administration of BMP7 has therapeutic potential in numerous rodent models of renal injury and disease. However, in the healthy kidney endogenous BMP7 ligand is vigorously counteracted by extracellular antagonists such as USAG1 and CHRDL1. Little is known about the degree of BMP signaling and the ligands driving it in the healthy adult kidney. In this study we characterize basal BMP signaling in the healthy tubular nephron, and show that BMP2 is expressed in proximal nephron epithelial cells. Comparative gene profiling of proximal tubule cell responses to BMP2 and BMP7 does not reveal any qualitative difference, suggesting that identical BMP gene targets may be activated in healthy and injured organs. Interestingly, our gene profiling analysis shows that BMP signaling activates a number of Notch regulated transcription factors, including HEY1. As in other biological systems, HEY1 functions as a negative feedback regulator of BMP2 expression in the proximal tubule. In summary, this work reveals endogenous BMP signaling patterns in the healthy human and mouse kidneys, and identifies novel gene targets, some of which are involved in the complex regulation of BMP signaling in the adult kidney. |
| Databáze: | OpenAIRE |
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