Activating transcription factor 3 (ATF3) promotes sublytic C5b-9-induced glomerular mesangial cells apoptosis through up-regulation of Gadd45α and KLF6 gene expression.

Abstract

The sublytic C5b-9 complexes can result in glomerular mesangial cells (GMCs) apoptosis, which involved in the initiation and development of rat Thy-1 nephritis. Activating transcription factor 3 (ATF3) is an immediate early gene for cells to cope with a variety of stress signals, and our previous study revealed that ATF3 could promote GMCs apoptosis attacked by sublytic C5b-9. But the mechanism of ATF3 promoting GMCs apoptosis triggered by sublytic C5b-9 attack has not been elucidated. In this study, the data showed that the expression of ATF3, growth arrest and DNA damage-45 alpha (Gadd45α), Krüppel-like factor 6 (KLF6) and proliferating cell nuclear antigen (PCNA) in the GMCs in response to sublytic C5b-9 stimulation for the indicated time was significantly increased, and ATF3 expression could lead to GMCs apoptosis through up-regulation of Gadd45α and KLF6, but not up-regulation of PCNA. Furthermore, Gadd45α was identified as a downstream target gene regulated by ATF3 directly, and KLF6 might be regulated by ATF3 in an indirect manner.

• Authors: Kuanfeng Xu, Ying Zhou, Wen Qiu, Xin Liu, Mei Xia, Lisha Liu, Xiaomei Liu, Dan Zhao, Yingwei Wang
• Journal: Immunobiology (Immunobiology) Vol. 216 Issue 8 Pg. 871-81 (Aug 2011) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 21396734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2011. Published by Elsevier GmbH. All rights reserved.

Chemical References

• Activating Transcription Factor 3
• Cell Cycle Proteins
• Complement Membrane Attack Complex
• Gadd45a protein, rat
• Klf6 protein, rat
• Kruppel-Like Factor 6
• Kruppel-Like Transcription Factors
• Nuclear Proteins
• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins
• RNA, Small Interfering
• Luciferases

Topics

• Activating Transcription Factor 3 (genetics, immunology, metabolism)
• Animals
• Apoptosis (immunology)
• Cell Cycle Proteins (genetics, immunology, metabolism)
• Cells, Cultured
• Complement Membrane Attack Complex (adverse effects, immunology, metabolism, pharmacology)
• DNA Damage
• Gene Expression
• Gene Silencing (drug effects)
• Kruppel-Like Factor 6
• Kruppel-Like Transcription Factors (genetics, immunology, metabolism)
• Luciferases (analysis)
• Mesangial Cells (cytology, immunology, metabolism)
• Nephritis (genetics, immunology, metabolism, pathology)
• Nuclear Proteins (genetics, immunology, metabolism)
• Plasmids
• Proliferating Cell Nuclear Antigen (genetics, immunology, metabolism)
• Proto-Oncogene Proteins (genetics, immunology, metabolism)
• RNA, Small Interfering (pharmacology)
• Rats
• Signal Transduction (genetics, immunology)
• Transcriptional Activation (immunology)
• Transfection
• Up-Regulation