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Estrogen Receptor αSignaling ExacerbatesImmune-MediatedNephropathies throughAlteration ofMetabolic Activity Chelsea CorradettiNeelakshi R. JogMatteo Cesaroni2017 год

Estrogen Receptor α Signaling Exacerbates Immune-Mediated Nephropathies through Alteration of Metabolic Activity
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Аннотация: Glomerulonephritis is one of the most serious manifestations of systemic lupus erythematous (SLE). Because SLE is ≥10 times more common in women, a role for estrogens in disease pathogenesis has long been suspected. Estrogen receptor α (ERα) is highly expressed in renal tissue. We asked whether ERα expression contributes to the development of immune-mediated nephropathies like in lupus nephritis. We tested the overall effects of estrogen receptors on the immune response by immunization with OVA and induction of chronic graft-versus-host disease in female ERα-knockout mice. We used nephrotoxic serum nephritis as a model of immune-mediated nephropathy. We investigated the influence of ERα on molecular pathways during nephritis by microarray analysis of glomerular extract gene expression. We performed RNA sequencing of lupus patient whole blood to determine common pathways in murine and human nephritis. Absence of ERα protects female mice from developing nephritis, despite the presence of immune complexes and the production of proinflammatory cytokines in the kidneys and normal humoral responses to immunization. Time-course microarray analysis of glomeruli during nephrotoxic serum nephritis revealed significant upregulation of genes related to PPAR-mediated lipid metabolism and downregulation of genes in the retinol metabolism in wild-type females compared with ERα-knockout females. Similarly, RNA sequencing of lupus patient blood revealed similar expression patterns of these same pathways. During nephritis, the altered activity of metabolic pathways, such as retinol metabolism, occurs downstream of ERα activation and is essential for the progression to end-stage renal failure.
Год издания: 2017
Авторы: Chelsea Corradetti, Neelakshi R. Jog, Matteo Cesaroni, Michael P. Madaio, Roberto Caricchio
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: Systemic Lupus Erythematosus Research, Renal Diseases and Glomerulopathies, Reproductive System and Pregnancy
Другие ссылки: The Journal of Immunology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)