Journal of Clinical and Cellular Immunology
Open Access

Sublytic C5b-9 triggers glomerular mesangial cell apoptosis in rat Thy-1 nephritis via Gadd45 activation mediated by Egr-1 and p300-dependent ATF3 acetylation

9^th European Immunology Conference Associated with Antibody Engineering Meeting

June 14-16, 2018 | Rome, Italy

Yingwei Wang, Fengxia He, Chenhui Zhao, Mengya Zhou, Tianyi Yu, Dan Zhao, Jing Zhang, Wen Qiu, Yanlai Lu, Yu Liu and Lulu Wang

Nanjing Medical University, China

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

The apoptosis of glomerular mesangial cells (GMCs) is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis (Thy-1N) and is accompanied by sublytic C5b-9 deposition. However, the mechanism by which sublytic C5b-9 triggers GMC apoptosis has not been elucidated. In this study, functional and histological examinations were performed on GMCs treated with sublytic C5b-9 (in vitro) and renal tissues of Thy-1N rats (in vivo). The in vitro studies found that sublytic C5b-9 could trigger GMC apoptosis through upregulating Egr-1, ATF3, and Gadd45 expression. Egr- 1-mediated post-transcriptional modulation of ATF3, Egr-1/ATF3-enhanced Gadd45 promoter activity, and p300-mediated ATF3 acetylation were all involved in GMC apoptosis. More importantly, the effective binding elements for Egr-1 and ATF3 to Gadd45�?²/�?³ promoters and the ATF3 acetylation site were identified. In vivo, silencing renal p300, Egr-1, ATF3, and Gadd45�?²/�?³ significantly decreased GMC apoptosis, secondary GMC proliferation, and urinary protein secretion in Thy-1N rats. Together, these findings implicate that sublytic C5b-9-induced activation of Egr-1/p300-ATF3/Gadd45 axis plays a critical role in GMC apoptosis in Thy-1N rats.

Biography :

Yingwei Wang is currently a Professor at Department of Immunology of Nanjing Medical University. She is conducting research in exploring the mechanisms of sublytic C5b-9-induced glomerular mesangial cell (GMC) apoptosis, inflammation and proliferation in mesangial proliferative glomerulonephritis (MsPGN) by using rat Thy-1 nephritis model. These include signal transduction, microRNA regulation, and transcriptional factor regulation. She is also exploring the effects of ubiquitination, acetylation and phosphorylation modification on the activation of signaling molecules, transcription factors and histones.