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

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

Immunobiology 2011 Aug

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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. Crown Copyright © 2011. Published by Elsevier GmbH. All rights reserved.

Citation

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