Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus

Publication date: May 2013 Source:Molecular Immunology, Volume 54, Issue 1 Author(s): Nicholas A. Young , Alexandra K. Friedman , Benjamin Kaffenberger , Murugesan V.S. Rajaram , Daniel J. Birmingham , Brad H. Rovin , Lee A. Hebert , Larry S. Schlesinger , Lai-Chu Wu , Wael N. Jarjour Systemic lupus erythematosus (SLE) is a prototypic, inflammatory autoimmune disease characterized by significant gender bias. Previous studies have established a role for hormones in SLE pathogenesis, including the sex hormone estrogen. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and β into the nucleus where they induce transcription by binding to estrogen response elements (EREs) of target genes. The ZAS3 locus encodes a signaling and transcriptional molecule involved in regulating inflammatory responses. We show that ZAS3 is significantly up-regulated in SLE patients at both the protein and mRNA levels in peripheral blood mononuclear cells (PBMCs). Furthermore, estrogen stimulates the expression of ZAS3 in vitro in several leukocyte and breast cancer cell lines of both human and murine origin. In vivo estrogen treatment mediates induction of tissue specific ZAS3 expression in several lymphoid organs in mice. Estrogen stimulation also significantly up-regulates ZAS3 expression in primary PBMCs, while treatment with testosterone has no effect. Mechanistically, estrogen induces differential ERα binding to putative EREs within the ZAS3 gene and ER...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research