Activating transcription factor 3 promotes sublytic C5b-9-induced glomerular mesangial cells apoptosis through up-regulation of Gadd45α and KLF6 (44.5)

Abstract

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, but the mechanism of sublytic C5b-9-mediated GMCs apoptosis remains unclear. 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. However, target genes of ATF3 in GMCs apoptosis triggered by sublytic C5b-9 stimulation have not been identified. 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 induced by sublytic C5b-9 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.