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

Kuanfeng Xu; Ying Zhou; Wen Qiu; Xin Liu; Mei Xia; Lisha Liu; Xiaomei Liu; Dan Zhao; Yingwei Wang

doi:10.1016/j.imbio.2011.02.005

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

Immunobiology. 2011 Aug;216(8):871-81. doi: 10.1016/j.imbio.2011.02.005. Epub 2011 Feb 22.

Authors

Kuanfeng Xu¹, Ying Zhou, Wen Qiu, Xin Liu, Mei Xia, Lisha Liu, Xiaomei Liu, Dan Zhao, Yingwei Wang

Affiliation

¹ Department of Microbiology and Immunology, Nanjing Medical University, 140 Nanjing Hanzhong Road, Nanjing, PR China.

PMID: 21396734
DOI: 10.1016/j.imbio.2011.02.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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